The document discusses the endocrine basis of normal pubertal development. It describes how puberty is regulated by the hypothalamic-pituitary-gonadal axis and the hormonal interactions involved in pubertal development in boys and girls. It also discusses adrenarche and the role of growth hormone in puberty. Key points include:
1) Puberty results from increased GnRH pulsatility from the hypothalamus, which activates the HPG axis.
2) Gonadotropins stimulate sex hormone production from the gonads, leading to secondary sex characteristics and gamete production.
3) Adrenarche involves increased adrenal androgen production starting in mid-childhood
What is puberty?
Puberty is the time in life when a person becomes sexually mature. It is a physical change that usually happens between ages 10 and 14 for girls and ages 12 and 16 for boys. Some African American girls start puberty earlier than white girls, making their age range for puberty 9 to 14.
Puberty starts when a part of the brain called the hypothalmus begins releasing a hormone called gonadotropin releasing hormone (GnRH).
GnRH then signals the pituitary gland to release two more hormones - luteinizing hormone (LH) and follicle-stimulating hormone (FSH) – to start sexual development.
A study funded in part by NICHD has identified a gene that appears to be the crucial signal for the beginning of puberty. Without a functioning copy of the gene, known as GPR54, humans appear unable to enter puberty normally.
Puberty & adolescence by Pandian M, Tutor, Dept of Physiology, DYPMCKOP,MHPandian M
Introduction
Components of puberty
Sudden spurt of physical growth
Appearance of secondary sex characters
Stages of development of secondary sex characters.
Types of secondary sex characters.
Hormonal changes during puberty
Control of onset of puberty
Applied aspects
Pediatrics notes about "Normal & Abnormal Puberty". These notes were published in 2018.
You can download them also from
- Telegram: https://t.me/pediatric_notes_2018
- Mediafire: http://www.mediafire.com/folder/u5u60m184t9z7/Pediatric_Notes_2018
Dickson Cv Akankwatsa is an ambitious 3rd year student at Bishop Stuart University, Uganda , pursuing a bachelor of Nursing science. More so, a HOSTEL councilor contestant 2016/17 in the same institution.
precocious puberty is one of the grey areas for pediatricians and gyenecologists. this is an attempt to answer some of the questions the content is references taken from authorative textbooks
What is puberty?
Puberty is the time in life when a person becomes sexually mature. It is a physical change that usually happens between ages 10 and 14 for girls and ages 12 and 16 for boys. Some African American girls start puberty earlier than white girls, making their age range for puberty 9 to 14.
Puberty starts when a part of the brain called the hypothalmus begins releasing a hormone called gonadotropin releasing hormone (GnRH).
GnRH then signals the pituitary gland to release two more hormones - luteinizing hormone (LH) and follicle-stimulating hormone (FSH) – to start sexual development.
A study funded in part by NICHD has identified a gene that appears to be the crucial signal for the beginning of puberty. Without a functioning copy of the gene, known as GPR54, humans appear unable to enter puberty normally.
Puberty & adolescence by Pandian M, Tutor, Dept of Physiology, DYPMCKOP,MHPandian M
Introduction
Components of puberty
Sudden spurt of physical growth
Appearance of secondary sex characters
Stages of development of secondary sex characters.
Types of secondary sex characters.
Hormonal changes during puberty
Control of onset of puberty
Applied aspects
Pediatrics notes about "Normal & Abnormal Puberty". These notes were published in 2018.
You can download them also from
- Telegram: https://t.me/pediatric_notes_2018
- Mediafire: http://www.mediafire.com/folder/u5u60m184t9z7/Pediatric_Notes_2018
Dickson Cv Akankwatsa is an ambitious 3rd year student at Bishop Stuart University, Uganda , pursuing a bachelor of Nursing science. More so, a HOSTEL councilor contestant 2016/17 in the same institution.
precocious puberty is one of the grey areas for pediatricians and gyenecologists. this is an attempt to answer some of the questions the content is references taken from authorative textbooks
Recent Trends in Pubertal Timing and Current Management of Precocious Puberty...Apollo Hospitals
Precocious puberty is defined as the development of pubertal signs at a younger age than the accepted lower limits for the onset of puberty. In girls, breast development before the age of 8 years, appearance of sexual pubic hair before the age of 8 years or beginning menses before the age of 9.5 years is traditionally considered as precocious puberty. This is accompanied by rapid growth rate, advanced skeletal maturation and increased levels of gonadotropins and/or sex steroids.
As a component of the endocrine system, both male and female gonads produce sex hormones. Male and female sex hormones are steroid hormones and as such, can pass through the cell membrane of their target cells to influence gene expression within cells. Gonadal hormone production is regulated by hormones secreted by the anterior pituitary in the brain. Hormones that stimulate the gonads to produce sex hormones are known as gonadotropins. The pituitary secretes the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These protein hormones influence reproductive organs in various ways. LH stimulates the testes to secrete the sex hormone testosterone and the ovaries to secrete progesterone and estrogens. FSH aids in the maturation of ovarian follicles (sacs containing ova) in females and sperm production in males.
Control mechanism of Female Reproductionsunitafeme
The menstrual cycle is the scientific term for the physiological changes that occur in fertile women for the purpose of sexual reproduction.The menstrual cycle is controlled by the endocrine system
Action of pituitary gland over growth harmone.Rajatmishra137
The pituitary gland is often called the master gland because it controls several other hormone glands in your body, including the thyroid and adrenals, the ovaries and testicles. ● It secretes hormones from both the front part (anterior) and the back part (posterior) of the gland. Hormones are chemicals that carry messages from one cell to another through your bloodstream.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
2. Article adolescent medicine
Normal Pubertal Development:
Part I: The Endocrine Basis of Puberty
Brian Bordini, MD,*
Objectives After completing this article, readers should be able to:
Robert L. Rosenfield, MD*
1. Explain how puberty is regulated by the hypothalamic-pituitary-gonadal axis.
2. Describe the hormonal interactions involved in pubertal development in boys and girls.
Author Disclosure
Drs Bordini and Introduction
Rosenfield have Puberty is a defining developmental stage of every child’s life, both physically and
disclosed no financial psychosocially. Concerns about the normalcy of pubertal development and menstrual
relationships relevant patterns are among the most common questions posed to every physician caring for
to this article. This children. This article reviews the primary physiologic changes in the hypothalamic-
pituitary-gonadal (HPG) axis and in adrenal androgen and growth hormone (GH)
commentary does not
production that underlie the normal pubertal milestones. Understanding of these changes
contain a discussion allows interpretation of laboratory data in children suspected of having pubertal abnor-
of an unapproved/ malities.
investigative use of a Puberty is the developmental stage during which a child becomes a young adult,
commercial product/ characterized by the maturation of gametogenesis, secretion of gonadal hormones, and
device. development of secondary sexual characteristics and reproductive functions. Adolescence is
used widely as a generally synonymous term for puberty, but the term often is used to
convey an added connotation of cognitive, psychological, and social change.
Thelarche denotes the onset of breast development, an estrogen effect. Pubarche
denotes the onset of sexual hair growth, an androgen effect. Menarche indicates the onset
of menses and spermarche the appearance of spermatozoa in seminal fluid. Gonadarche
refers to the onset of pubertal function of the gonads, which produce most of the sex
hormones that underlie the pubertal changes in secondary sex characteristics. Adrenarche
refers to the onset of the adrenal androgen production that contributes to pubarche.
The Hormonal Axes Underlying Puberty
The Hypothalamic-Pituitary-Gonadal Axis
Normal puberty results from sustained, mature activity of the HPG axis. (1). The major
hormones of the HPG axis are shown in Figure 1. In response to a single gonadotropin-
releasing hormone (GnRH), the pituitary gland releases two gonadotropins: luteinizing
hormone (LH) and follicle-stimulating hormone (FSH). GnRH is secreted by specialized
neurons of the hypothalamus in a pulsatile fashion. Pituitary LH and FSH secretion
consequently is pulsatile and can be sustained only in response to pulsatile GnRH signals.
LH acts primarily on the specialized interstitial cells of the gonads to stimulate formation
of androgens, and FSH acts primarily on the follicular/tubular compartment to stimulate
formation of estrogen from androgen precursors, inhibin,
and gametes. The function of the two compartments of the
gonads is coordinated by paracrine regulatory mechanisms.
Abbreviations The HPG axis is active during three phases of develop-
ACTH: adrenocorticotropic hormone ment: fetal, neonatal, and adult, with puberty being the
DHEAS: dehydroepiandrosterone sulfate period of transition to mature function. Changes in GnRH
FSH: follicle-stimulating hormone secretion underlie the changing activity of the HPG axis. The
GH: growth hormone sexually dimorphic patterns of sex hormone secretion during
GnRH: gonadotropin-releasing hormone the prenatal and neonatal periods of HPG activity appear to
HPG: hypothalamic-pituitary-gonadal play a role in programming sexually dimorphic patterns of
LH: luteinizing hormone behavior, metabolism, and neuroendocrine function in later
life.
*Section of Adult and Pediatric Endocrinology, The University of Chicago Pritzker School of Medicine, Chicago, IL.
Pediatrics in Review Vol.32 No.6 June 2011 223
3. adolescent medicine pubertal development
ingly active again in the late prepubertal period, as central
nervous system restraint recedes, followed by an increas-
ing tempo throughout puberty.
The gonads account for the most important circulat-
ing estrogen (estradiol) and androgen (testosterone).
Gonadal function accounts for more than 90% of estra-
diol production in the female (50% in the male) and more
than 90% of testosterone production in the male (50% in
the female) (Fig. 2). (4)(5)
Figure 1. The hypothalamic-pituitary-gonadal axis. Hypo-
thalamic neurons release gonadotropin-releasing hormone
(GnRH) into the pituitary portal venous system, where it stimu-
lates gonadotropin (luteinizing hormone [LH] and follicle-
stimulating hormone [FSH]) secretion. LH primarily stimulates
specialized interstitial cells (theca cells in the ovary or Leydig cells
in the testes) to secrete androgens. FSH primarily stimulates the
ovarian follicle or seminiferous tubules to form estrogen, inhibin,
and gametes (eggs or sperm). The interstitial and follicular/
tubular compartments act cooperatively through paracrine
mechanisms to form estrogen and to regulate sex steroid and
gamete development. Sex steroids exert endocrine closed-loop
negative feedback effects on GnRH and gonadotropin secretion.
Inhibin exerts negative feedback on FSH secretion. In mature
females, a critical estradiol concentration for a critical duration
exerts a transient positive feedback effect to stimulate the LH
surge that initiates ovulation.
The HPG axis is established during the first trimester.
Its activity in the second trimester contributes to the
establishment of normal penile size and the inguinal-
scrotal phase of testicular descent. (2)(3) In the latter half Figure 2. Simplified diagram of sex steroid production by
of pregnancy, activity is suppressed by the high estrogens the adult adrenal glands, follicular phase ovaries, and testes.
elaborated by the fetoplacental unit. Blood production rates shown are the sum of direct secretion
The HPG axis promptly functions at a pubertal level (heavy solid arrows) and peripheral formation from secreted
in the newborn after withdrawal from maternal estro- precursors (dotted arrows). Several key steroidogenic enzyme
gens. This “minipuberty of the newborn” is subclinical, activities expressed in these glands, such as sulfotransferase
except for contributing to genital growth, acne, and (SULT), 3 -hydroxysteroid dehydrogenase (3 ), aromatase,
transient thelarche in the neonate. and 17 -hydroxysteroid dehydrogenase type 5 (17 HSD5),
are also expressed in peripheral tissues such as liver, fat, and
HPG function subsequently comes under gradual
skin. Type 3 17 HSD (17 HSD3) is only expressed in testes.
central nervous system restraint at the end of the neo-
Peripheral conversion from secreted androstenedione accounts
natal period. The axis is relatively, but not absolutely, for 50% of testosterone in women, and about 10% of estra-
dormant throughout childhood, particularly in girls, diol and DHEAS similarly arise from circulating precursors.
who have slightly higher FSH concentrations than boys Estrone, the intermediate in the pathway from androstenedione to
and a few ultrasonographically visible ovarian follicles as estradiol, is not shown. DHEA dehydroepiandrosterone, DHEAS
evidence of this effect. The HPG axis becomes increas- dehydroepiandrosterone sulfate, A’DIONE androstenedione
224 Pediatrics in Review Vol.32 No.6 June 2011
4. adolescent medicine pubertal development
Adrenarche, the “Puberty” of the insulin-like growth factor-I concentrations to peaks in
Adrenal Gland late puberty that are above those of adults, sometimes in
Adrenarche is actually a re-onset of adrenal androgen the adult acromegalic range. Half of the characteristic
production. The fetal zone of the adrenal cortex elabo- pubertal growth spurt is due to the direct effect of sex
rates large amounts of dehydroepiandrosterone sulfate steroids on epiphyseal growth and half to GH stimula-
(DHEAS), which is important as the major substrate for tion. Conversely, in accord with the general principle
placental estrogen formation during pregnancy. This that everything grows better with GH, GH is necessary
zone then regresses over the first several postnatal for optimal gonadotropin effects on gonadal growth and
months. sex steroid effects on secondary sex characteristics. For
Adrenarche is the pseudopuberty of the adrenal gland example, selective GH resistance is characterized by small
that begins in mid-childhood as the zona reticularis of testes and micropenis, poor breast and sexual hair devel-
the adrenal cortex develops. (1) This zone has the capac- opment, and absence of a pubertal growth spurt. (12)
ity to form 17-ketosteroids, but not cortisol, in response
to adrenocorticotropic hormone (ACTH), and DHEAS Regulation of the Onset and Progression
is the primary endpoint of this biosynthetic pathway. of Puberty
Consequently, although cortisol concentrations and the There is no single “trigger” for puberty; rather, puberty
cortisol response to ACTH do not change from child- results from a gradual increase in GnRH pulsatility that
hood to adulthood, DHEAS values gradually rise from arises from maturation of central nervous system devel-
mid-childhood until adulthood. This timeframe coin- opmental programs that send inhibitory and stimulatory
cides approximately with the gonadal androgen produc- signals to GnRH neurons. (1) Puberty is associated with
tion of true puberty, but adrenarche is an incomplete changing sensitivity of the neuroendocrine system to
aspect of puberty that is independent of pubertal matu- negative feedback by gonadal hormones. When GnRH
ration of the HPG axis. The adrenal gland secretes more secretory activity is low due to central nervous system
than 90% of DHEAS in children and women and more inhibition in mid-childhood, it is inhibited by trace
than 70% in adult men, while 50% of testosterone in the amounts of sex steroids. Increasing central activation
female and less than 10% of testosterone in the male is during puberty permits sex steroids to rise to adult con-
produced by the adrenal. (6) Adrenal androgen concen- centrations before exerting negative feedback effects.
trations increase to a point sufficient to stimulate apo- The major GnRH-inhibitory systems are GABAergic
crine odor and mild acne after about 5 years of age and and opioidergic; the major excitatory systems involve
pubic hair growth after about 10 years of age (Table). glutamate and kisspeptin, with glial cells facilitating
GnRH secretion. Kisspeptin is a hypothalamic neuro-
Interactions Between Pubertal Hormones and peptide discovered in the search for the molecular basis
the Growth Hormone/Insulin-like Growth of hypogonadotropic hypogonadism; it acts as an im-
Factor-I Axis portant signal for pubertal GnRH release via GPR54, a
Pituitary GH secretion increases during puberty in re- G-protein coupled receptor located on GnRH neurons.
sponse to sex steroids. (1) This rise in GH causes a rise in It has been estimated that at least half of the varia-
Table. Typical Early Morning Pubertal Hormone Blood Concentrations
LH FSH Estradiol TT DHEAS
Group (IU/L) (IU/L) (pg/mL) (ng/dL) ( g/dL)
Prepubertal 1 to 5 yr <0.3 <4.0 <10 <20 5 to 40*
Premenarchal females <12 1.0 to 12 <50 13 to 44 35 to 130
Postmenarchal females** 2.0 to 11 1.0 to 12 20 to 85 15 to 59 75 to 255
Adult men*** 1.4 to 9.0 1.0 to 9.2 <60 300 to 950 100 to 460
DHEAS dehydroepiandrosterone sulfate, FSH follicle-stimulating hormone, LH luteinizing hormone, TT total testosterone
Conversions to SI units: estradiol 3.61 pmol/L, testosterone 0.0347 nmol/L, DHEAS 0.0271 mol/L
Assay-specific ranges may vary.
*Prepubertal children 6 to 9 years of age may have adrenarchal DHEAS values up to approximately 70 g/dL
**Early follicular phase values given; mid-cycle LH up to 85 IU/L, FSH up to 19 U/L, estradiol up to 350 pg/mL
***Pubertal males values are between and overlap with prepubertal and adult male values
Data from Bordini et al, (7) Mortensen et al, (8) Zimmer et al, (9) Mayo Clinical Laboratories, (10) Esoterix Laboratory Services. (11)
Pediatrics in Review Vol.32 No.6 June 2011 225
5. adolescent medicine pubertal development
tion in the timing of puberty is genetically determined, pulsatile secretion during sleep (Fig. 3). (18)(19) In
and ethnicity is one such factor. (1)(13) Sex hormones, response to nocturnal LH secretion, the pattern of go-
hormonally active environmental chemicals (“environmen- nadal sex steroid secretion differs between the sexes:
tal disruptors”), (14) diverse somatic stimuli (including ovarian secretion of estradiol peaks in mid-day and tes-
nutrition, the growth hormone/insulin-like growth factor ticular secretion of testosterone peaks promptly during
system, thyroid hormones), and general health all affect the sleep. In addition, girls’ pubertal hormone secretion is
pubertal process. subclinically cyclic from early puberty. As puberty pro-
Pubertal and skeletal maturation appear to have com- gresses, LH secretion persists further into the daytime.
mon somatic determinants. Children generally enter pu- After menarche, this diurnal variation no longer exists.
berty when they achieve a pubertal bone age. Pubertal Adult sex steroid concentrations, however, have a mild
stage normally correlates better with the bone age than diurnal variation, being highest on awakening.
with chronologic age. (15) Thus, for example, the onset The two gonadotropins each act primarily on specific
of breast development normally occurs at a bone age of gonadal cell types. LH stimulates the interstitial cells of
about 10 years and menarche occurs at a bone age of about the ovaries (theca cells) to form androgenic precursors of
12.5 years, whether the child is 9 or 14 years of age. estradiol and those of the testes (Leydig cells) to secrete
Optimal nutrition is necessary for initiation and main- testosterone itself. FSH acts on the sex cord derivatives of
tenance of normal reproductive function. The hypothesis the ovary (granulosa cells) and testes (Sertoli cells) to
that a critical amount of body fat is the weight-related stimulate gametogenesis and gonadal growth. In granu-
trigger for pubertal development originated with the dis- losa cells, FSH strongly stimulates aromatase to form
covery by Frisch and coworkers that weight correlated with estradiol from thecal androgens.
pubertal growth and menarche better than it did with As the gonads become increasingly sensitized to
chronologic age or height. (16) Early to mid-childhood gonadotropin stimulation, they grow and secrete sex
may be a critical period for weight to influence the onset of hormones at steadily increased rates. Within 3 years of
puberty. (17) Suboptimal nutrition related to socioeco- rising above the prepubertal range, estradiol increases an
nomic conditions is an important factor in the late onset of average of 20 pg/mL (73.4 pmol/L) yearly to reach the
puberty in underdeveloped countries. Conversely, obesity is mid-adult range and testosterone increases an average of
an important factor in advancing the onset of puberty in 100 ng/dL (3.47 nmol/L) yearly to reach the lower
United States girls. (13) adult range (Table). (20) These concentrations then
Leptin, a hormone secreted by fat cells, appears to be gradually induce their effects. The hormonal increases
an important link between nutrition and the attainment culminate in positive feedback in girls, which refers to the
and maintenance of reproductive competence. (1) Lep- female neuroendocrine system becoming capable of se-
tin acts on the hypothalamus to reduce appetite and creting a mid-cycle surge of LH when the ovary signals
stimulate gonadotropin secretion. Leptin deficiency that it is prepared for ovulation via a critical and sustained
causes obesity and gonadotropin deficiency. Blood leptin level of estrogen secretion.
concentrations rise throughout childhood and puberty Estrogen stimulates the classic female target tissues:
to reach higher values in girls than boys. Attainment of a the female genital tract (eg, endometrial growth, cervical
critical threshold appears to signal that nutritional stores mucus secretion) and breasts. Androgen stimulates the
are sufficient for mature function of the GnRH pulse classic male target tissues (eg, sexual hair and sebaceous
generator and, thus, permits puberty. gland). Both stimulate sexual drive and function. Both
Although prolactin and pineal gland hormones affect sex steroids account for the pubertal growth spurt, di-
puberty in lower animals and can cause pubertal disor- rectly and indirectly via growth hormone. Both directly
ders in humans, neither has a clear role in normal human stimulate epiphyseal growth and epiphyseal maturation,
puberty. which is indexed by bone age radiographs and peak bone
mass accrual. (21) However, they differ in some of their
Hormonal Changes of Normal Puberty effects on skeletal growth. Androgen is responsible for
The first hormonal change of puberty is a sleep-related the wider bones (the laryngeal enlargement accounting
increase in the pulsatile release of LH by the pituitary for the pubertal voice change), while estrogen is ulti-
gonadotropes. FSH is secreted in parallel but increases mately necessary for epiphyseal fusion and is the more
relatively less. At the beginning of puberty, a unique potent inhibitor of bone resorption. They also affect
diurnal variation of pubertal hormones occurs, with little growth of a wide variety of other somatic tissues. During
LH secretion during the day and a significant increase in puberty, estrogen promotes lipogenesis and lower body
226 Pediatrics in Review Vol.32 No.6 June 2011
6. adolescent medicine pubertal development
Figure 4. Diagram of average gonadotropin and sex steroid
concentrations during the normal menstrual cycle. The data
are centered in reference to days before ( ) or after ( ) the
day of the mid-cycle surge of luteinizing hormone (LH). The
gonadotropin concentrations are typical of polyclonal radio-
immunoassay, and the baseline values are about twice as high
as those obtained by current monoclonal assays. M menses
begin, E2 estradiol, PROG progesterone. Reprinted with
permission from Rosenfield et al. (1)
fat distribution. In contrast, androgens generally are
lipolytic, although they favor the development of visceral
fat stores, and promote muscular development. The sim-
ilar increase of body mass index during puberty in girls
Figure 3. Pubertal hormone rhythms. In an early pubertal girl and boys, thus, is due to differences in body composition,
(top panel), luteinizing hormone (LH) secretion is minimal with a higher percent being body fat in girls and lean
during waking hours. Pubertal LH pulsations promptly begin body mass in boys. (22)
with sleep onset and wane with sleep offset, followed several The menstrual cycle arises from cyclic maturation of
hours later by increased ovarian estradiol secretion that peaks ovarian follicles that result in cyclic changes in sex hor-
mid-day. Reprinted with permission from Boyar et al. (18) mones, particularly estradiol and progesterone, which
Copyright 1976, The Endocrine Society. In an early pubertal
entrain cyclic changes in gonadotropin concentrations
boy (bottom panel), daytime LH values are low, with minimal
(Fig. 4). The biologic goal of this monthly variation is to
testosterone secretion. Pubertal LH pulsations begin promptly
with sleep onset and cease with sleep offset; testosterone select and nurture one dominant follicle to the point of
secretion occurs primarily during sleep, beginning about ovulation for potential fertilization. A normal average
2 hours after LH increases and waning on awakening. Re- 28-day cycle consists of two phases: the follicular phase
printed with permission from Judd et al. (19) Copyright 1974, (variable in duration, averaging 14 days at maturity) and
The Endocrine Society. Panels are modified by aligning times. the luteal phase (14 1 SD days), with the latter occur-
This figure demonstrates the clinical importance of consider- ring only in ovulatory cycles. The follicular phase begins
ing diurnal and pulsatile hormone secretion in evaluating with the onset of menses and culminates in the mid-cycle
pubertal status. First, because of diurnal rhythmicity, daytime LH surge, which induces ovulation from the follicle. The
hormone values during early puberty are not representative empty follicle forms the corpus luteum, initiating the
of the 24-hour production of pubertal hormones, as indicated
luteal phase. Progesterone increases steadily to be sus-
for LH in this girl (breast stage 3) and for testosterone and
tained at very high levels for several days, along with
gonadotropins in this boy (stage 2). Second, because of the
episodic pulsatile nature of gonadotropin and sex steroid lesser but substantial increases in estradiol. Progesterone
secretion, hormone values may differ markedly within 1 hour. and estradiol secretion from the corpus luteum maintain
The gonadotropin concentrations were determined by early- the endometrial layer of the uterus in preparation for
generation radioimmunoassays, and the baseline values are potential pregnancy. If pregnancy does not occur, with
higher than those obtained by current assays. its resultant increase in human chorionic gonadotropin,
Pediatrics in Review Vol.32 No.6 June 2011 227
7. adolescent medicine pubertal development
the corpus luteum life span is exhausted, which results References
in withdrawal of female sex steroids, followed by endo- 1. Rosenfield RL, Cooke DW, Radovick S. The ovary and female
metrial sloughing and menstrual flow. maturation. In: Sperling M, ed. Pediatric Endocrinology. 3rd ed.
Philadelphia, PA: Elsevier; 2008:530 – 609
Assessment of pubertal hormone concentrations re-
2. Rosenfield RL, Lucky AW, Allen TD. The diagnosis and man-
quires reliable hormone assays in addition to consideration agement of intersex. Curr Probl Pediatr. 1980;10:1– 66
of the diurnal changes of early puberty and cyclic changes in 3. Thorup J, McLachlan R, Cortes D, et al. What is new in
girls. Although early pubertal children have greater average cryptorchidism and hypospadias—a critical review on the testicular
hormone concentrations than prepubertal children, their dysgenesis hypothesis. J Pediatr Surg. 2010;45:2074 –2086
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of the fetus, child, and adolescent. Adv Pediatr. 1972;19:171–213
(7)(8)(9)(10)(11) The widely available, older generation of
5. Kelch RP, Jenner MR, Weinstein R, Kaplan SL, Grumbach MM.
polyclonal antibody-based radioimmunoassays for gonado- Estradiol and testosterone secretion by human, simian, and canine
tropins do not possess sufficient sensitivity and specificity testes, in males with hypogonadism and in male pseudohermaph-
for optimal diagnosis of pubertal disorders. The modern rodites with the feminizing testes syndrome. J Clin Invest. 1972;
multichannel platform assays available in many community 51:824 – 830
hospitals are generally adequate for these purposes, as in- 6. de Peretti E, Forest MG. Pattern of plasma dehydroepian-
drosterone sulfate levels in humans from birth to adulthood: evi-
dicated by sensitivities of 0.1 to 0.15 U/L for LH and
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FSH. These platform assays are also reliable for DHEAS 572–577
assays. On the other hand, platform assays are very unreli- 7. Bordini BD, Littlejohn EE, Rosenfeld RL. Blunted sleep-related
able for measuring testosterone and estradiol at the rela- LH rise in healthy premenarcheal pubertal girls with elevated body
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women. The practitioner should not order these tests unless 8. Mortensen M, Ehrmann DA, Littlejohn E, Rosenfield RL.
Asymptomatic volunteers with a polycystic ovary are a functionally
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Daytime pubertal hormone concentrations may not utility of intermittent short-acting GnRH agonist administration in
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diurnal and cyclic variations (Fig. 3). For this reason, 10. Mayo Medical Laboratories. Reference Laboratory Services for
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Accessed March 2011 at: www.mayomedicallaboratories.com
pubertal disorders. A peak LH value greater than approx- 11. Esoterix Laboratory Services. Endocrinology Expected Values
imately 4.0 U/L in response to GnRH or GnRH agonist and S.I. Unit Conversion Table. Calabasas Hills, CA: Esoterix
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• The exact mechanisms that awaken the HPG axis Clinical review: constitutional advancement of growth, a.k.a. early
from its childhood quiescence remain unknown, but growth acceleration, predicts early puberty and childhood obesity.
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PIR Quiz
Quiz questions also available online at http://pedsinreview.aappublications.org.
1. Which of the following statements about normal puberty in children is true?
A. Bone age correlates better with pubertal development than chronologic age.
B. Gonadotropin-releasing hormone (GnRH) secretion in response to negative feedback from sex steroids is
constant throughout life.
C. Growth hormone secretion is the sole determinant of the pubertal growth spurt.
D. Menarche is the first stage of puberty in girls.
E. Normal pubertal development is unrelated to nutritional status.
2. Which of the following statements best describes adrenarche?
A. Breast development becomes evident in girls.
B. Hypothalamic production of adrenocorticotropin hormone increases.
C. Maternal estrogens are withdrawn, causing neonatal acne.
D. Spermatozoa begin to appear in seminal fluid.
E. The adrenal gland increases production of dehydroepiandrosterone sulfate.
3. Which of the following is the primary action of luteinizing hormone?
A. Secretion of follicle-stimulating hormone.
B. Secretion of GnRH from the pituitary gland.
C. Stimulation of gametogenesis in the testes.
D. Stimulation of the gonads to produce androgens.
E. Stimulation of the ovarian follicle to produce estrogen.
4. At which of the following phases of the menstrual cycle is the concentration of progesterone the highest?
A. The beginning of the follicular phase.
B. The beginning of the luteal phase.
C. The end of the luteal phase.
D. The middle of the follicular phase.
E. The middle of the luteal phase.
HealthyChildren.org Parent Resources from AAP
The reader is likely to find material to share with parents that is relevant to this article by
visiting this link: http://www.healthychildren.org/English/ages-stages/gradeschool/
puberty/Pages/default.aspx.
Pediatrics in Review Vol.32 No.6 June 2011 229
9. Normal Pubertal Development: Part I: The Endocrine Basis of Puberty
Brian Bordini and Robert L. Rosenfield
Pediatr. Rev. 2011;32;223-229
DOI: 10.1542/pir.32-6-223
Updated Information including high-resolution figures, can be found at:
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