1. Hypothalamus and Pituitary

2. 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.

3. Hypothalamus and Pituitary
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: 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.

5. Anterior pituitary: adenohypophysis
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).

6. Hypothalamus and pituitary gland

7. Hypothalamus and pituitary gland

8. Regulation of Hypothalamus

9. Anatomical and functional organization

10. Hypothalamic releasing factors for anterior pituitary hormones
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 hormones
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. Characteristics of hypothalamic releasing hormones
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
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).

14. Anterior pituitary cells and hormones

15. Hypothalamus and anterior pituitary

16. Anterior pituitary hormones

17. 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.

18. Hypothalamus-pituitary axis

19. Feedback control

20. Feedback control of thyroid function

21. Feedback and restoration of homeostasis

22. Feedback control of growth hormone

23. Growth hormone vs. metabolic state
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. Growth hormone vs. metabolic state
During fasting, GH antagonizes insulin action and helps mediate glucose sparing, ie stimulates gluconeogenesis
In general, duing 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

25. Growth hormone and metabolic state

26. 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

27. ACTH synthesis

28. ACTH 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. 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
JFK had Addison’s disease and was treated with cortisol injections

30. b-endorphin 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

31. Regulation of ACTH secretion

32. Regulation of ACTH 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. 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

34. Regulation of ACTH

35. 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
Adrenogenital syndrome: masculization of female fetus

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

38. 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

39. LH/FSH 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

40. Pulsitile secretion of GnRH and LH

41. Regulation of LH/FSH 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. Regulation of LH/FSH
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. 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

44. Regulation of gonadotropin secretion

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

46. Feedback control of thyroid function

47. Lacotrophs 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 is TRH
Ocytocin also stimulates prolactin release
Estradiol enhances prolactin synthesis

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

49. Posterior pituitary hormones: ADH (AVP) and Oxytocin (really hypothalamic hormones)
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

50. Hypothalamus and posterior pituitary

51. Structures of ADH and oxytocin

52. Oxytocin: stimulates myoepithelial contractions
In uterus during parturition
In mammary gland during lactation

53. Oxytocin: 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.

54. Oxytocin: 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, parturition, and coitus
Estrogen increases synthesis and lowers threshold for release

55. Oxytocin secretion is stimulated by nursing

56. 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

57. Regulation of ADH secretion

58. ADH increases renal tubular absorption of water

59. ADH and plasma osmolality

60. ADH and blood pressure