2. Hypothalamus and Pituitary

3. Hypothalamus and Pituitary
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.

4. 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

5. ANTERIOR PITUITARY HORMONES
Six major hormones are secreted by the adenohypophysis,
or anterior pituitary gland

6. Hormones of the hypothalamus and the anterior pituitary gland
TRH, thyrotropin releasing hormone; CRF, corticotropin releasing hormone;
GnRH, gonadotropin releasing hormone; LH, luteinizing hormone; FSH, follicle-stimulating hormone;
TSH, thyroid-stimulating hormone; ACTH,adrenocorticotropic hormone; IGF-1, insulinlike growth factor 1.

7. Anterior pituitary: adenohypophysis
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).

8. Posterior Pituitary: neurohypophysis
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.

9. Hypothalamic releasing hormones Travel to specific cells in anterior pituitary to stimulate synthesis and secretion of trophic hormones
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

10. ANTERIOR PITUITARY HORMONES

11. Anterior pituitary hormones

12. Growth Hormone
Growth hormone, or somatotropin, is a protein that stimulates linear body growth in children and regulates cellular metabolism in both adults and children
stimulates lipolysis, enhances production of free fatty acids, elevates blood glucose
Enhance production of an insulinlike growth factor (IGF-1)
Growth hormone
is released during sleep, with maximum release occurring
an hour after the onset of sleep.

13. Increases markedly during stress
Prolactin
In women, prolactin acts with other hormones on the mammary gland during pregnancy to develop lactation and after birth to
maintain it.
Hyperprolactinemia causes impotence in men and amenorrhea and infertility in women
Prolactin serum levels increase during pregnancy and breast-feeding, at least immediately after the birth.
Increases markedly during stress
increases
markedly during stress

14. There is no known therapeutic use for prolactin, but
serum levels are measured to diagnose hyperprolactinemia
Approximately one-third of women who need treatment for infertility have high serum prolactin levels.
Hyperprolactinemia has been traditionally
treated by the dopaminergic agonist bromocriptine
(Parodel)

15. Lacotrophs Site of production of prolactin
Lactogenesis (milk synthesis) requires prolactin
Dopamine inhibits prolactin
Prolactin releasing hormone is TRH
Ocytocin also stimulates prolactin release
Estradiol enhances prolactin synthesis

16. ACTH: adrenocorticotropic hormone: synthesis and regulation of secrtion
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

17. Thyroid-Stimulating Hormone
TSH, or thyrotropin, is a glycosylated protein of two
subunits, and .
TSH stimulates the thyroid gland to produce thyroid hormones.
Deficiencies are treated by giving thyroxine itself rather than TSH,
but TSH is available for diagnostic purposes to differentiate between pituitary and thyroid gland failure as causes of hypothyroidism

18. Thyrotrophs Site of TSH synthesis
Pattern of secretion is relatively steady
TSH secretion stimulated by TRH
Feedback control by T3 (thyroid hormone)

19. Feedback control of thyroid function

20. ACTH Adrenocorticotropic hormone (ACTH), or corticotropin
ACTH is made up of 39 amino acids
Regulates adrenal cortex and synthesis of adrenocorticosteroids
Overproduction of ACTH may accompany increased pigmentation due to a-MSH.
ACTH stimulates

21. Feedback regulation of hypothalmus/pituitary
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. Feedback control

24. Addison’s Disease
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
he zona fasciculata constitutes the middle zone of the adrenal cortex, sitting directly beneath the zona glomerulosa

25. Regulation of ACTH
ACTH stimulates production of glucocorticoids from the adrenal cortex
Stimulation of release
CRH and ADH
Stress
Hypoglycemia
CRH and ADH both synthesized in hypothalamus
Vasopressin, also known as antidiuretic hormone (ADH)
Corticotropin-releasing hormone (CRH) 

26. ACTH 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

27. Regulation of ACTH

28. is easier and less expensive to treat patients having It
is easier and less expensive to treat patients having
adrenocortical insufficiency with glucocorticoid replacement
therapy than it is to use ACTH
Therefore,
use of ACTH (Acthar) is restricted to diagnosis;

29. ACTH 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

30. Gonadotropins Follicle-stimulating hormone (FSH),
luteinizing hormone(LH),
human chorionic gonadotropin (hCG)
TSH
they have
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

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

32. Gonadotrophs 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

33. LH/FSH LH and FSH are pituitary hormones secreted in pulsatile
fashion approximately every 2 hours.
In women before menopause, this pattern is superimposed on much larger changes that occur during the normal menstrual cycle
FSH is released in substantial amounts during the follicular phase of the menstrual cycle
Required for proper development of ovarian follicles and for estrogen synthesis from granulosa cells of the ovary

34. Regulation of LH/FSH Negative feed-back
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.
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

35. Regulation of LH/FSH Positive feedback
Estradiol at high plasma concentrations in late follicular phase of ovarian cycle stimulates GnRH and LH surge– triggers ovulation

36. HYPOTHALAMIC REGULATORY
HORMONES
Five peptides isolated from the hypothalamus regulate
release of one or more pituitary hormones. In addition,
dopamine released from the hypothalamus inhibits prolactin production.

37. Somatostatin
Somatostatin (or somatotropin release–inhibiting factor [SRIF]) occurs primarily as a 14–amino acid peptide, although a 28–amino acid form also exists
Somatostatin inhibits the secretion of many substances in addition to growth hormone
not useful clinically
Inhibition of secretion of
Growth hormone, Thyroid-stimulating hormone, Prolactin
ACTH, Insulin, Glucagon, Pancreatic polypeptide
Gastrin

38. Thyrotropin-Releasing Hormone
Thyrotropin-releasing hormone, or protirelin, consists
of three amino acids.
TRH (Relefact TRH) is used for tests to distinguish primary from secondary hypothyroidism
Gonadotropin-Releasing Hormone
GnRH (gonadorelin, luteinizing hormone–releasing
hormone)
is a decapeptide that stimulates production
of LH and FSH. It is released in bursts from the hypothalamus
at regular intervals, about every 2 hours,
The pituitary gland responds
to these regular pulses by producing LH and FSH

39. Posterior pituitary hormones: ADH (AVP) and Oxytocin
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

40. Oxytocin: stimulates myoepithelial contractions
In uterus during parturition
In mammary gland during lactation
milk ejection from lactating mammary gland
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.
uterine contractions
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

41. ADH: conserve body water and regulate tonicity of body fluids
Also known as vasopressin
Regulated by osmotic and volume stimuli
Water deprivation increases osmolality of plasma which activates hypothalmic osmoreceptors to stimulate ADH release