Hypothalamus and Pituitary

2.  The hypothalamus-pituitary unit is the most
dominant portion of the entire endocrine
system.
 The output of the hypothalamus-pituitary
unit regulates the function of the thyroid,
adrenal and reproductive glands and also
controls somatic growth, lactation, milk
secretion and water metabolism.

3.  Pituitary function depends on the hypothalamus
and the anatomical organization of the
hypothalamus-pituitary unit reflects this
relationship.
 The pituitary gland lies in a pocket of bone at the
base of the brain, just below the hypothalamus to
which it is connected by a stalk containing nerve
fibers and blood vessels. The pituitary is composed
to two lobes-- anterior and posterior

4.  Posterior pituitary: an outgrowth of the
hypothalamus composed of neural tissue.
 Hypothalamic neurons pass through the
neural stalk and end in the posterior pituitary.
 The upper portion of the neural stalk extends
into the hypothalamus and is called the
median eminence.

5.  Anterior pituitary: connected to the hypothalamus
by the superior hypophyseal artery.
 The antererior pituitary is an amalgam of hormone
producing glandular cells.
 The anterior pituitary produces six peptide
hormones: prolactin, growth hormone (GH),
thyroid stimulating hormone (TSH),
adrenocorticotropic hormone (ACTH), follicle-
stimulating hormone (FSH), and luteinizing
hormone (LH).

10.  Travel to adenohypophysis via hypophyseal-portal
circulation
 Travel to specific cells in anterior pituitary to
stimulate synthesis and secretion of trophic
hormones

11. Hypothalamic releasing hormone Effect on pituitary
Corticotropin releasing hormone
(CRH)
Stimulates ACTH secretion
Thyrotropin releasing hormone
(TRH)
Stimulates TSH and Prolactin
secretion
Growth hormone releasing
hormone (GHRH)
Stimulates GH secretion
Somatostatin Inhibits GH (and other hormone)
secretion
Gonadotropin releasing hormone
(GnRH)
Stimulates LH and FSH
secretion
Prolactin releasing hormone (PRH) Stimulates PRL secretion
Prolactin inhibiting hormone
(dopamine)
Inhibits PRL secretion

12.  Secretion in pulses
 Act on specific membrane receptors
 Transduce signals via second messengers
 Stimulate release of stored pituitary hormones
 Stimulate synthesis of pituitary hormones
 Stimulates hyperplasia and hypertophy of target
cells
 Regulates its own receptor

13.  Anterior pituitary: connected to the hypothalamus
by hypothalmoanterior pituitary portal vessels.
 The anterior pituitary produces six peptide
hormones:
 prolactin, growth hormone (GH),
 thyroid stimulating hormone (TSH),
 adrenocorticotropic hormone (ACTH),
 follicle-stimulating hormone (FSH),
 luteinizing hormone (LH).

17.  A prominent feature of each of the hormonal
sequences initiated by the hypothalamic
releasing hormones is negative feedback
exerted upon the hypothalamic-pituitary
system by the hormones whose production
are stimulated in the sequence.

23.  When protein and energy intake are adequate, it is
appropriate to convert amino acids to protein and stimulate
growth. hence GH and insulin promote anabolic reactions
during protein intake.
 During carbohydrate intake, GH antagonizes insulin effects--
blocks glucose uptake to prevent hypoglycemia. (if there is
too much insulin, all the glucose would be taken up).
 When there is adequate glucose as during absorptive phase,
and glucose uptake is required, then GH secretion is inhibited
so it won't counter act insulin action.

24.  During fasting, GH antagonizes insulin action and helps
mediate glucose sparing, ie stimulates gluconeogenesis.
 In general, during anabolic or absorptive phase, GH
facilitates insulin action, to promote growth.
 during fasting or post-absorptive phase, GH opposes insulin
action, to promote catabolism or glucose sparing

26.  Produced in corticotrophs
 ACTH is produced in the anterior pituitary by
proteolytic processing of Prepro-opiomelanocortin
(POMC).
 Other neuropeptide products include b and g
lipotropin, b-endorphin, and a-melanocyte-
stimulating hormone (a-MSH).
 ACTH is a key regulator of the stress response

28.  ACTH is made up of 39 amino acids
Regulates adrenal cortex and synthesis of
adrenocorticosteroids
a-MSH resides in first 13 AA of ACTH
a-MSH stimulates melanocytes and can darken
skin
Overproduction of ACTH may accompany
increased pigmentation due to a-MSH.

29.  Disease in which patients lack cortisol from
zona fasiculata, and thus lacks negative
feedback that suppresses ACTH production
 Result: overproduction of ACTH
 Skin color will darken
 JFK had Addison’s disease and was treated
with cortisol injections

30.  Produced as a result of ACTH synthesis
 Binds to opiate receptors
 Results in “runner’s high”
 Role in anterior pituitary not completely
understood
 One of many endogenous opiods such as
enkephalins

32.  Stimulation of release
 CRH and ADH
 Stress
 Hypoglycemia
 CRH and ADH both synthesized in hypothalamus
 ADH is released by posertior pituitary and reaches anterior
pituitary via inferior hypophyseal artery.

33.  Circadian pattern of release
 Highest levels of cortisol are in early AM following
ACTH release
 Depends on sleep-wake cycle, jet-lag can result in
alteration of pattern
 Opposes the circadian pattern of growth
hormone secretion

35.  Acts on adrenal cortex
 stimulates growth of cortex (trophic action)
 Stimulates steroid hormone synthesis
 Lack of negative feedback from cortisol results in
aberrantly high ACTH, elevated levels of other
adrenal corticosteroids– adrenal androgens
 Adrenogenital syndrome: masculization of female
fetus

36.  LH, FSH,TSH and hCG
a and b subunits
Each subunit encoded by different gene
 a subunit is identical for all hormones
 b subunit are unique and provide biological
specificity

37. Glycoprotein hormones contain two subunits, a
common a subunit and a distinct b subunit:
TSH, LH, FSH and hCG.

38.  Cells in anterior pituitary that produce LH and FSH
 Synthesis and secretion stimulated by GnRH– major
effect on LH
 FSH secretion controlled by inhibin
 Pulsitile secretion of GnRH and inhibin cause
distinct patterns of LH and FSH secretion

39.  Pulsatile pattern of secretion
 LH pulses are biphasic (every 1 minute, then large pulse at
1 hour)
 FSH pulses are uniphasic
 Diurnal– LH/FSH more pronounced during puberty
 Cyclic in females– ovarian cycle with LH surge at
time of ovulation
 Males are not cyclic, but constant pulses of LH cause
pulses of testosterone to be produced

41.  Negative feed-back
 Inhibin produced by testes and ovaries Decreases FSH b-
subunit expression
 Testosterone from Leydig cells– synthesis stimulated by
LH, feedsback to inhibit GnRH production from
hypothalamus and down-regulates GnRH receptors
 Progesterone– suppresses ovulation, basis for oral
contraceptives. Works at both the level of pituitary and
hypothalamus.

42.  Dopamine, endorphin, and prolactin inhibit GnRH
release.
 Prolactin inhibition affords post-partum contraceptive
effect
 Overproduction of prolactin via pituitary tumor can
cause amenorrhea– shuts off GnRH
 Treated with bromocryptine (dopamine agonist)
 Surgical removal of pituitary tumor

43.  Positive feedback
 Estradiol at high plasma concentrations in late
follicular phase of ovarian cycle stimulates GnRH
and LH surge– triggers ovulation

45.  Site ofTSH synthesis
 Pattern of secretion is relatively steady
 TSH secretion stimulated byTRH
 Feedback control byT3 (thyroid hormone)

47.  Site of production of prolactin
 Lactogenesis (milk synthesis) requires prolactin
 Tonically inhibited
 Of the anterior pituitary hormones, the only one
 Multifactoral control, balance favors inhibition
 Dopamine inhibits prolactin
 Prolactin releasing hormone isTRH
 Oxytocin also stimulates prolactin release
 Estradiol enhances prolactin synthesis

48.  Stimulates breast development and
lactogenesis
 May be involved in development of Leydig
cells in pre-pubertal males
 Immunomodulatory effects– stimulatesT cell
functions
 Prolactin receptors in thymus

49.  Both are synthesized in the cell bodies of
hypothalamic neurons
 ADH: supraoptic nucleus
 Oxytocin: paraventricular nucleus
 Both are synthesized as preprohormones and
processed into nonapeptides (nine amino acids).
 They are released from the termini in response to an
action potential which travels from the axon body in
the hypothalamus

52.  In uterus during parturition
 In mammary gland during lactation

53.  suckling is major stimulus for release.
 sensory receptors in nipple connect with
nerve fibers to the spine, then impulses are
relayed through brain to PVN where
cholinergic synapses fire on oxytocin
neurons and stimulate release.

54.  Reflexes originating in the cervical, vaginal
and uterus stimulate oxytocin synthesis and
release via neural input to hypothalamus
 Increases in plasma at time of ovulation,
parturition, and coitus
 Estrogen increases synthesis and lowers
threshold for release

56.  Also known as vasopressin
 Regulated by osmotic and volume stimuli
 Water deprivation increases osmolality of
plasma which activates hypothalmic
osmoreceptors to stimulate ADH release