9. Androgens
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9
Development of secondary sex
characters
Testes are responsible for male
characters
Testes Functions:
1. Spermatogenesis occuring within the
seminiferous tubules
2. Production of Androgenic hormones
11. Testosterone
from cholesterol by Leydig cells in testes
Secreted at 1st trimester1, during neonatal life2, continually after puberty3
Converted by 5 α-reductase to the more potent, 5α-dihydrotestosterone
(DHT),
Binds and activates androgen receptor (AR)
Bound in plasma to albumin & SHBG sex hormone binding globulin
AR present in reproductive tissue, skeletal muscle, brain, kidney etc.
1 2 3
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15. Biological Effects
Testes:
• Promotion of spermatogenesis and maturation of sperm
• high dose causes testicular atrophy by inhibiting Gn secretion
Androgenic Effects:
in foetus, development of male reproductive tract – internal
genitalia, vas deferens, epididymis and external genitalia
in puberty, development of :
– primary sexual characteristics (penis enlargement, scrotum and testes)
– secondary sexual characteristics (male body shape, axillary / pubic hair,
deeper pitch voice, thickening of skin – greasy, loss of subcutaneous fat)
Adulthood: Baldness, BHP, Prostatic cancer
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16. anabolic effects
n Pubertal growth – both boy and girl
n Bone growth – thickness and length
n Oestrogen from testosterone –bones fuse
and mineralization
n Muscle building – by exercise
n Positive nitrogen, minerals and water balance
–in weight increase
n appetite Increase
n Acceleration of erythropoiesis
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18. Mechanism of Action
Androgen receptor:
n testosterone and DH testosterone – act via AR
n Ligand binding and DNA binding domains
n Mutations in AR: Incomplete sexual development
u Kennedy`s disease: in spinal and bulbar muscle atrophy
Estrogen Receptor:
• Teststerone converts to
estrogen by CYP19
• Deficiency of CYP19
and estrogen receptor –
failure to fuse long bones,
osteoporosis etc.
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19. T DHT DHT- R
T- R
R
R
T- R
Nucleus
90%
10%
5- reductase
cytoplasm
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20. Pharmacokinetics
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20
Absorption: undergoes high first pass metabolism.
Therefore IM injections or synthetic preparations are
used
Transport: highly protein bound
(98%, SHBG, albumin)
Metabolism:
by liver enzymes : androsterone & etiocholanolone
excretion by urine
small quantity of oestrogen also produced from testosterone
24. n Steroid family ..Regulates reproductive system…. Creates muscle mass
n Regulates metabolism and immune function…. fluidity of cell membrane
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25. Baby’s Testosterone
Functions
male secondary sex characteristics (muscle, hair, bone..
preventing Osteoporosis)
reproductive organs (testes and prostate), sperm, and body
Stimulates blood flow
Health and well being
Creates sex drive
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26. How testosterone affects my life
Although I do not have as much testosterone as
estrogen in my body (because I am a girl), I still have
it. It is produced in the ovaries and adrenal
glands…
Testosterone effects by:
Creating muscle mass
Creating sex drive ( after 21 or marriage, when it is ok to
have kids)
Improving my mood ( studies in women)
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39. Mood & General
Well being
Testosterone 80 mg/day in
Elderly men with low plasma
Testosterone Improved
general well-being
after 3 months
HRT in Young hypogonadal
men improves mental Activity.
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41. Diabetic Patient with ED
HRT in Type 2 D
with
Androgen Deficiency
Improves
Glucose homeostasis,
body composition
& ED.
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42. Reproduces
testosterone naturally
Chest, back and legs Workout
.. boost testosterone,
makes your body fit
1. Exercise
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over exercise affect
negatively …
reduce
testosterone.
42
44. Exercise / Rest
Lift heavy-weights … four to six reps on every exercise.
do three to four sets
Don’t do same exercise every day.
2 days gap before working the same muscle.
Rest sufficiently. 2 days off
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45. 2. Alcohol
Alcohol effects directly on
testis
.. after 5 drinks,
44% less testosterone
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“Alcohol is responsible for
aging and heart problems”
affects growth hormone as
well.
45
46. 3. Stress / Sleep
/ Smoking
“ sleep and stress reducing
medication or yoga”
“Eight hours sleep build testosterone ”
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Smoking…. reduces
testosterone
production
46
48. 8/3/2022 48
Sleep early.
Yoga is your best friend
Avoid smoking
control of your breathing
Laugh … relax
control your temper
deal people nicely
49. 4. Sex
“ activity may
increase the
production of
testosterone”
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59. Danazol effective orally
Weak androgenic, anabolic, progestational & glucocorticoid action
– Induces androgen specific mRNA production
suppresion of Gn (FSH and LH) secretion from Pituitary
– FSH & LH release …inhibition of testicular/ovarian function
– endometrial atrophy and ammenorrhoea
Uses:
– Endometriosis Menorrhagia Fibrocystic breast disease
– Hereditary angioneurotic oedema Gynecomastia Infertility
Side effects:
• Amenorrhea (High doses)
• Androgenic effects - Decreased breast size, hirsutism, weight
gain etc.
• Hot flashes, night sweating, cramps
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60. Cyproterone acetate
Progesterone like activity – inhibits LH causing
antiandrogenic action
Competes with dihydrotestosterone for intracellular
receptor
Uses:
Ca prostate – to prevent flare up with LHRH
Male pattern baldness
Hirusitism
Virilizing syndrome
Precocious puberty
Hot flushes in male
Acne
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61. Flutamide
Non-steroidal and no hormonal activity
specific antiandrogenic action
Active metabolite “2-hydroxyflutamide”
causes competitive block Androgen action –
Accessory sex organs
Pituitary
Uses:
Cancer of prostate along with GnRH agonist
Female hirusitism
Dose: 250 mg tds.
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62. Finasteride
► MOA: Competitive inhibitor of 5 α-reductase
Selective of 5 α-reductase type-2 isoenzyme
Mainly acts on urogenital tract (prostate) – DHT level
lowered but not plasma Testosterone level
► Uses:
1. Benign prostatic hypertrophy – decrease in prostate
volume, improved urinary flow, reversion of disease
progression
– Withdrawal results in regrowth – prolonged therapy
2. Male pattern baldness
–
– Side effects:
– loss of libido, impotence, decreased ejaculation
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67. Two cellular mechanism of action :
1- androgen receptor
Free testosterone is transported to target tissue cells,
binds androgen receptor, reduced to DHT by 5-alpha
reductase.
DHT binds receptor strongly than testosterone,
HREs (hormone response elements ) influence
transcription. androgenic effects.
68. A-Sexual Function
intrauterine life : secreted from genital ridge
male sex characters as :
Formation of penis , scrotum , seminal
vesicles , prostate , male genital ducts
Suppression of female genital organs
descent of testes into scrotum 2nd month of
pregnancy
69. Metabolic effects
1- increases basal metabolic rate
2- anabolic: increases muscle bulk and strength
3- glycogenolysis, increase glucose uptake by cells
4- reduction of ca2+ and po4
5- union of epiphysis
6- stimulate erythropoiesis
Degraded by conjugation in liver
excreted in urine or in bile salts
70.
71. Control :
1- Luteinizing hormone : the hormone secretion
is stimulated by LH
2- GnRH : LH secretion is stimulated by “ GnRH
“ from hypothalamus to the ant. Pituitary
3- _ve feedback mechanism : mainly by the
testosterone on the hypothalamus and weaker
effect on the ant. Pituitary
Other factors affects secretion : weight loss ,
zinc deficiency , aging. dominance challenge ,
sleep, training , licorice , antiandrogens
72.
73.
74. Uses
primary hypogonadism (Testicular dysfunction)
Secondary hypogonadism (Failure of hypothalamus
or pituitary)
increase lean body mass and muscle strength
Antiaging hormone (DHEA)
Performance Enhancer.
76. Adverse Effects
Virilization:
women getting androgens for estrogen-dependent
mammary carcinoma
Cholestatic Jaundice
Priapism (sustained erection)
Oligospermia
Oedema--via promotion of salt and water retention
Precocious puberty and short stature Acne
Hepatic carcinoma
Gynaecomastia
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77. Adverse Effects
1. females:
Androgens can cause masculinization, acne,
growth of facial hair, deepening of the voice,
male pattern baldness, and excessive muscle
development. Menstrual irregularities may also
occur.
,
males:
Excess androgens can cause priapism Impotence,
decreased spermatogenesis, and gynecomastia.
Cosmetic changes such as those
described for females may occur as well. Androgens
can also stimulate growth of the prostate.
78. children
Androgens can cause abnormal sexual maturation
and growth disturbances resulting from
premature closing of the epiphyseal plates.
General effects:
Androgens can increase serum LDL and lower
serum high-density lipoprotein levels. Whether
these changes in the lipid profile predispose
patients to heart disease is unknown. Androgens
can also cause fluid retention, leading to edema.
Continue…….
79. Male Hypogonadism
1- fetal life: testes are not functioning , none of male
characteristics appear , instead female organs are
formed
2- boy loses testes before puberty :
A state of eunichism : infantile sex organs and sex
characters
Slightly tall because of slower union of epiphysis
3- Man is castrated after puberty:
- secondary sexual characters aren’t affected
-decreased sexual desire and sterility
-accessory sexual organs are gradually dysfunctioned
-FSH & LH are increased due to –ve feedback
mechanism
80. B- adiposogenitial syndrome, Frolich’s
syndrome, hypothalamic eunuchism
Hypogona
dism due to
genetic
inability of
hypothalam
us to
secrete
normal
amount of
Gnrh &
abnormality
of feeding
of center of
81.
82. fun facts :
1-A mother's testosterone level during pregnancy is correlated with her
daughter's sex-
.
2-Falling in love decreases men's testosterone levels while increasing women's
testosterone levels
3- Fatherhood also decreases testosterone levels in men, suggesting that the
resulting emotional and behavioral changes promote paternal care.
4- Men with less testosterone are more likely to be in love and married. while
those who produce more are likely to be divorced .
5- When testosterone and endorphins in semen meet the cervical wall, females
receive a spike in testosterone, endorphin, and oxytocin levels, and males have
increased endorphins and oxytocin.
6-Testosterone levels play a major role in risk-taking during financial decisions.
7- Brain in males are larger and have more myelinated fibers
Penile erection occurs when blood swells the corpus cavernosum, an effect facilitated by relaxation of regional smooth muscle. Smooth muscle tone is regulated by cellular Ca2+, which activates the Ca2+/calmodulin (CaM)-dependent enzyme myosin light chain kinase (MLCK), which leads to MLC phosphorylation and contraction. The nitric oxide (NO) pathway leads to relaxation of smooth muscle by stimulating the soluble guanylyl cyclase (sGC), which results in the production of cyclic GMP (cGMP) and the activation of cGMP-dependent protein kinase (PKG). PKG causes smooth-muscle relaxation by mechanisms that are still being defined and that might include a reduction in cytosolic Ca2+ (by enhanced Ca2+ export and/or by reduced inositol trisphosphate (InsP3) receptor-mediated Ca2+ mobilization) and dephosphorylation of myosin light chains (by activation of MLC phosphatase and/or by sequestration of MLCK in a phosphorylated form that is not readily activated by Ca2+/CaM). Viagra® specifically inhibits the breakdown of cellular cGMP by PDE5 (an isoform of phosphodiesterase that is localized to erectile tissue), and thereby prolongs and enhances the effects of NO/cGMP.
