physiology of the human pituitary+gland.pptx

the physiology of the pituitary gland

1. Pituitary gland

2. Anatomy of pituitary gland Called Hypophysis 0.5 to 1 g in wt Situated in a pocket of the sphenoid bone at the base of the brain called sella turcica. Diaphragma sellae – deflection of durameter that closes the cavity Has 2 portions- adenohypophysis and neurohypophysis

3. Embroyology Anterior pituitary develops from Rathkes pouch which is a upward outpouching of roof of oral cavity Posterior pituitary develops from downward outpouching from brain in the floor of 3 rd ventricle

4. Blood supply Posterior pituitary – supplied mainly by inferior hypophyseal artery  capillary plexus  dural sinus Anterior pituitary – supplied by superior hypophyseal artery which forms two plexuses Primary plexus –lies in median eminence Secondary plexus – lies in anterior pituitary gland

5. Neurohypophysis Neurovascular structure Parts – Pars nervosa Infundibulum Median eminence Contains axonal processes, glial like cells called pituicytes along with fenestrated capillaries Hormones released – 1.Antidiuretic hormone(vasopressin) 2.Oxytocin

6. Cell bodies of axonal processes are located in supraoptic nuclei and paraventricular nuclei of hypothalamus Cell bodies are magnocellular that project axons as hypothalamohypophysial tracts

7. Adenohypophysis Anterior portion of the gland Parts – 1. Pars tuberalis 2. Pars distalis 3. Pars intermedia Made of interlacing cell cords and fenestrated sinusoidal capillaries Has 5 types of cells that secrete 6 hormones collectively called anterior pituitary hormones

8. Cell types of anterior pituitary

9. Hypothalamo pituitary axes (endocrine axes) Each endocrine axis is composed of three levels of endocrine cells: 1 . Hypothalamic neurons, 2 . Anterior pituitary cells, and 3 . Peripheral endocrine glands .

10. First level – hypothalamic neurons Hypophysiotropic region in hypothalamus(parvicellular) Project axons to median eminence Release releasing or inhibitory hormones at median eminence They enter primary plexus and carried by long portal veins to secondary plexus in ant pituitary They diffuse out and stimulate or inhibit specific cell type in ant pituitary

11. Hypothalamic hormones Corticotropin releasing hormone – corticotropes Thyrotropin releasing hormone – thyrotropes Gonadotropin releasing hormone – gonadotropes Growth hormone releasing hormone – stimulatory to somatotropes Growth hormone inhibitory hormone( Somatostatin) – inhibitory to somatotropes Dopamine – inhibitory to lactotropes ? Prolactin releasing factor – stimulatory to lactotropes

12. Second level – ant pituitary hormones Hormone Target gland Adrenocorticotropic hormone Adrenal cortex Thyroid stimulating hormone Thyroid gland Follicle stimulating hormone Ovary and testis Luteinizing hormone Ovary and testis Growth hormone Liver Prolactin No target gland

13. The lactotrope differs from the other endocrine cell types of the adenohypophysis in two major ways: The lactotrope is not part of an endocrine axis. This means that PRL acts directly on nonendocrine cells (primarily of the breast) to induce physiological changes. Production and secretion of PRL are predominantly under inhibitory control by the hypothalamus.

14. Third level – peripheral endocrine glands Hormone Target gland Hormones Adrenocorticotropic hormone Adrenal cortex Cortisol , aldosterone Thyroid stimulating hormone Thyroid gland Triodo thyronine,tetraiodothyronine Follicle stimulating hormone Ovary and testis Estrogen , progesterone, testosterone and inhibin Luteinizing hormone Ovary and testis Growth hormone Liver Insulin like growth factor ( IGF 1 & IGF 2 ) Prolactin No target gland NONE

15. Hypothalamic-pituitary-adrenal (HPA) axis Hypothalamic neuron Primary plexus Secondary plexus CRH Corticotrope ACTH ADRENAL LONG LOOP SHORT LOOP

16. Hypothalamic-pituitary-testis and hypothalamic pituitary ovary axis Hypothalamic neuron Primary plexus Secondary plexus GNRH Gonadotrope FSH AND LH TESTIS OR OVARY LONG LOOP SHORT LOOP

17. Hypothalamic-pituitary-thyroid axis Hypothalamic neuron Primary plexus Secondary plexus TRH Thyrotrope TSH Thyroid LONG LOOP SHORT LOOP

18. Hypothalamic-pituitary-liver axis Hypothalamic neuron Primary plexus Secondary plexus GHRH Somatotrope GH LIVER LONG LOOP SHORT LOOP IGF

19. Features of endocrine axes The activity of a specific axis is normally maintained at a set point Hypothalamic hypophysiotropic neurons are often secreted in a pulsatile manner Abnormally low or high levels of a peripheral hormone (e.g., thyroid hormone) may be due to a defect at the level of the peripheral endocrine gland (e.g., thyroid), the pituitary gland, or the hypothalamus. Such lesions are referred to as primary, secondary, and tertiary endocrine disorders, respectively

20. Summary Anterior pituitary lobe Posterior pituitary lobe Epithelial tissue Neural tissue Has neurovascular connection with hypothalamus Has neural connection with hypothalamus Hormones synthesized by specific cell types in gland itself Hormones are synthesized in hypothalamic neurons & transported to gland Part of endocrine axes - Hypothalamic releasing or inhibitory hormones control secretion of ant pit hormones -

21. Anterior pit hormones Hypothalamic hormone Cell type Ant pit hormone CRH CORTICOTROPE ACTH TRH THYROTROPE TSH GNRH GONADOTROPE FSH, LH GHRH SOMATOTROPE GH SOMATOSTATIN SOMATOTROPE INHIBIT GH RELEASE DOPAMINE LACTOTROPE INHIBIT PRL RELEASE PRF LACTOTROPE PRL

22. Anterior pituitary hormones

23. Feedback control of growth hormone

24. Regulation of Growth Hormone Secretion GH secretion controlled primarily by hypothalamic GHRH stimulation and somatostatin inhibition Neurotransmitters involved in control of GH secretion– via regulation of GHRH and somatostatin

25. Neurotransmitter systems that stimulate GHRH and/or inhibit somatostatin Catecholamines acting via a 2-adrenergic receptors Dopamine acting via D1 or D2 receptors Excitatory amino acids acting via both NMDA and non-NMDA receptors Regulation of Growth Hormone Secretion

26. b -adrenergic receptors stimulate somatostatin release and inhibit GH b -adrenergic receptors inhibit hypothalamic release of GHRH Regulation of Growth Hormone Secretion

27. 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.

28. 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 Growth hormone vs. metabolic state

29. Growth hormone and metabolic state

30. Clinical assessment of GH Random serum samples not useful due to pulsatile pattern of release Provocative tests necessary GH measurement after 90 min exercise GH measurement immediately after onset of sleep Definitive tests GH measurement after insulin-induced hypoglycemia Glucose suppresses GH levels 30-90 min after administration– patients with GH excess do not suppress Measurement of IGF-1 to assess GH excess

31. Acromegaly and Gigantism Caused by eosinophilic adenomas of somatotrophs Excess GH leads to development of gigantism if hypersecretion is present during early life– a rare condition Symmetrical enlargement of body resulting in true giant with overgrowth of long bones, connective tissue and visceral organs. Excess GH leads to acromegaly if hypersecretion occurs after body growth has stopped. Elongation of long bones not possible so there is over growth of cancellous bones– protruding jaw, thickening of phalanges, and over growth of visceral organs

32. Acromegaly A) before presentation; B) at admission Harvey Cushing’s first reported case Acromegaly

33. Gigantism Identical twins, 22 years old, excess GH secretion

34. ACTH: adrenocorticotropic hormone: synthesis and regulation of secretion 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

35. ACTH synthesis Processing and cleavage of pro-opiomelanocortin (POMC) ACTH

36. 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.

37. Melanocyte-stimulating hormone (MSH) MSH peptides derived by proteolytic cleavage of POMC a -MSH has antipyretic and anti-inflammatory effects Also inhibits CRH and LHRH secretion Four MSH receptors identified May inhibit feeding behavior ACTH has MSH-like activity However– MSH has NO ACTH like activity

38. Regulation of ACTH secretion

39. Regulation of ACTH secretion Stimulation of release CRH and ADH Stress Hypoglycemia CRH and ADH both synthesized in hypothalamus ADH (a.k.a. vasopressin) is released by posterior pituitary and reaches anterior pituitary via inferior hypophyseal artery.

40. 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

41. Regulation of ACTH

42. 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

43. 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

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

45. 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

46. 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

47. Pulsitile secretion of GnRH and LH

48. 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.

49. 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 Regulation of LH/FSH

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

51. Regulation of gonadotropin secretion

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

53. Feedback control of thyroid function

54. 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

55. 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

56. Clinical assessment of PRL Single basal serum PRL measurement sufficient to determine excess PRL deficiency not a usual clinical concern PRL is only anterior pituitary with predominant negative control by hypothalamus– often elevated by lesions that interfere with portal blood flow. Elevated by primary PRL adenomas of pituitary

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

58. Structures of ADH and oxytocin

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

60. 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 .

61. 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

62. POSTERIOR PIT HORMONES OXYTOCIN ADH ( VASOPRESSIN )