16. pituitary gland

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16. pituitary gland

  1. 1. The Hypothalamic-Pituitary Axis and Pituitary Hormones
  2. 2. The hypothalamus , a region of the brain that controls an immense number of bodily functions, is located at the base of the brain. The pituitary gland , also known As hypophysis , lies immediately below the hypothalamus. It rests in a depression at The base of the skull, called sella turcica . Pituitary gland <ul><li>Anterior pituitary (adenohypophysis) </li></ul><ul><li>- cells secrete peptide/protein hormones </li></ul><ul><li>Posterior pituitary (neurohypophysis) </li></ul><ul><li>- is an extension of the hypothalamus </li></ul><ul><li>- is composed largely of the axons of the hypothalamic neurons </li></ul><ul><li>In many mammals, there is also an intermediate lobe (pars intermedia) between the </li></ul><ul><li>anterior and posterior pituitary </li></ul>
  3. 3. <ul><li>Based on histologic features, both the adenohypophysis and neurohypophysis are subdivided: </li></ul><ul><li>- Adenohypophysis </li></ul><ul><li>- pars distalis </li></ul><ul><li>- pars tuberalis (contains hypophyseal vessels) </li></ul><ul><li>- pars intermedia (secretes melanocyte-stimulating hormone [MSH]) </li></ul><ul><li>- Neurohypophysis </li></ul><ul><li>- pars nervosa </li></ul><ul><li>- median eminence (the upper section of neurohypophysis) </li></ul><ul><li>- infundibular stalk (the “stem” that connects the pars nervosa to the bas of the brain) </li></ul><ul><li>Secretion of hormones from anterior pituitary is under strict control of the hypothalamic </li></ul><ul><li>releasing/inhibiting hormones which reach the anterior pituitary through </li></ul><ul><li>Hypothalamic-hypophyseal portal vessels that branch again into a series of capillaries </li></ul><ul><li>within the adenohypophysis. </li></ul>
  4. 6. <ul><li>Three distinct cell types are seen in the adenohypophysis: </li></ul><ul><li>Acidophils (40%) </li></ul><ul><li>- somatotrophs – produce growth hormone (GH) </li></ul><ul><li>- lactotrophs – produce prolactin (PRL) </li></ul><ul><li>Basophils (10%) </li></ul><ul><li>- thyrotrophs - produce thyroid stimulating hormone (TSH) – a glycoprotein </li></ul><ul><li>- gonadotrophs – produce luteinizing hormone (LH) & follicle – stimulation </li></ul><ul><li>hormone (FSH) – glycoproteins </li></ul><ul><li>- corticotrophs – produce adrenocorticotropic hormone (ACTH) – polypeptide </li></ul><ul><li>Chromophobes (50%) </li></ul>
  5. 7. <ul><li>The major portion of the neurohypophysis contains unmyelinated axons from </li></ul><ul><li>hypothalamic neurosecretory neurons: </li></ul><ul><li>Supraoptic nuclei – mainly produce antidiuretic hormone (ADH)/vasopressin (AVP) </li></ul><ul><li>+ neurophysin </li></ul><ul><li>Paraventricular nuclei – mainly produce oxytocine + neurophysin </li></ul>
  6. 8. Anterior pituitary hormones (six peptide hormones)
  7. 9. <ul><li>Growth hormone (GH/somatotropin) </li></ul><ul><li>Synthesized and secreted by somatotrophs </li></ul><ul><li>Stimulates body growth </li></ul><ul><li>- GH liver/other tissues IGF 1 (insulin-like growth factor-1) </li></ul><ul><li>chondrocytes (cartilage cells) long bone growth </li></ul><ul><li>- IGF 1 also differentiation & prolifiration of myoblasts muscle growth </li></ul><ul><li>Metabolic effects (on protein, lipid & carbohydrate metabolism) </li></ul><ul><li>- IGF 1 amino acid uptake protein synthesis + oxidation of protein </li></ul><ul><li>- IGF 1 glucose synthesis in the liver </li></ul><ul><li>- GH (direct action) adipocytes (fat cells) free fatty acids </li></ul><ul><li>-GH (anti-insulin/direct action) uptake of glucose in peripheral tissues </li></ul><ul><li>glucose in plasma insulin in plasma (hyperinsulinemia) </li></ul>
  8. 10. Control of GH secretion <ul><li>GHRH (growth hormone-releasing hormone), a hypothalamic peptide synthesis + secretion of GH </li></ul><ul><li>Stress, exercise, hypoglycemia, sleep GH </li></ul><ul><li>Ghrelin , a peptide secreted y stomach GH </li></ul><ul><li>Somatostatin (hypothalamic growth hormone inhibiting hormone) GH synthesis+release </li></ul><ul><li>IGF 1 somatostatin GH </li></ul><ul><li>GH GH ( autocrine negative feedback ) </li></ul><ul><li>Release of hormone is pulsatile </li></ul>
  9. 11. Clinical (hyposecretion/hypersecretion) <ul><li>Site of lesion may be at the level of: </li></ul><ul><li>- the hypothalamus </li></ul><ul><li>- the pituitary </li></ul><ul><li>- target cells </li></ul><ul><li>Deficiency in GH/receptor defects growth retardation or dwarfism </li></ul><ul><li>GH secretion in young children/adolescents (from tumor of somatotrophs) </li></ul><ul><li>giantism </li></ul><ul><li>GH secretion in adults acromegaly </li></ul>
  10. 12. <ul><li>Thyroid-stimulating hormone (thyrotropin/TSH) </li></ul><ul><li>Secreted by “thyrotrophs” of the anterior pituitary </li></ul><ul><li>- a glycoprotein hormone </li></ul><ul><li>- a compound of α and β subunits </li></ul><ul><li>Thyrotropin-releasing hormone (TRH) from the hypothalamus </li></ul><ul><li>thyrotrophs thyrotropin (TSH) </li></ul><ul><li>TSH thyroid thyroid hormones (T 3 & T 4 ) </li></ul><ul><li>T 3 and T 4 in plasma TRH action on thyrotrophs T 3 & T 4 levels </li></ul><ul><li>negative feedback at anterior pituitary thyrotrophs ) + hypothalamus </li></ul><ul><li>Stress/dopamine/cortisol/somatostatin TSH </li></ul>
  11. 14. Adrenocorticotropic hormone (ACTH/corticotropin) <ul><li>Secreted by the anterior pituitary “corticotrophs” </li></ul><ul><li>Corticotropin releasing factor (CRF) from the hypothalamus corticotrophs </li></ul><ul><li>corticotropin ( ACTH ) </li></ul><ul><li>CRF proopiomelanocortin ACTH + β-lipotropin + α-MSH </li></ul><ul><li>ACTH adrenal glucocorticoids (cortisol) </li></ul><ul><li>cortisol CRF ACTH ( negative feedback ) </li></ul><ul><li>β -lipotropin – precursor of β-endorphin </li></ul><ul><li>β -endorphin – opioid peptide that alleviates pain </li></ul><ul><li>MSH – controls melanin pigmentation in the skin </li></ul><ul><li>Corticotrophs adenomas ACTH cortisol secondary Cushing’s </li></ul><ul><li>disease </li></ul>Clinical
  12. 16. Gonadotropins (FSH and LH) <ul><li>Secreted by pituitary “gonadotrophs” </li></ul><ul><li>Hypothalamic GnRH gonadotrophs LH (luteinizing hormone) and </li></ul><ul><li>FSH (follicle-stimulating hormone) </li></ul><ul><li>LH sex steroid (testosterone in males and estrogenes + progesterone in females) </li></ul><ul><li>LH follicle induces ovulation corpus luteum (luteinization) pro- </li></ul><ul><li>gesterone + estrogenes </li></ul><ul><li>FSH maturation of ovarian follicles in females and spermatogenesis in males </li></ul><ul><li>FSH inhibin both in males and females </li></ul><ul><li>Inhibin FSH secretion at the pituitary level ( negative feedback ) </li></ul><ul><li>Estrogens/testosterone LH secretion ( negative feedback ) </li></ul><ul><li>LH & FSH secretions are pulsatile </li></ul>Clinical <ul><li>Attenuated secretion of LH/FSH or both results in hypogonadism </li></ul><ul><li>- in males low sperm count </li></ul><ul><li>- in females cessation of reproductive cycles </li></ul><ul><li>Elevated blood levels of LH and FSH or both usually reflect lack of gonadal steroid </li></ul><ul><li>negative feedback </li></ul>
  13. 18. Prolactin <ul><li>A single-chain protein hormone closely related to growth hormone </li></ul><ul><li>It is secreted by “lactotrophs” of the anterior pituitary </li></ul><ul><li>Also secreted by the “deciduas” of the pregnant uterus </li></ul><ul><li>Prolactin induces lobuloalveolar growth of the mammary gland ( during pregnancy </li></ul><ul><li>and lactation ) </li></ul><ul><li>Prolactin stimulates lactogenesis after giving birth to a baby – in the presence of </li></ul><ul><li>cortisol&insulin , prolactin produces milk proteins </li></ul><ul><li>In some mammals ( rodents, dogs, skunks ) prolactin is necessary to maintain </li></ul><ul><li>pregnancy by maintaining their luteal function. In mice , prolactin deficiency </li></ul><ul><li>blocks ovulation, fertilization, implantation and thus makes the animals infertile </li></ul><ul><li>Experimental evidences suggest that prolactin may act as autocrine/paracrine </li></ul><ul><li>modulator of immune activity </li></ul><ul><li>Prolactin-inhibiting factor (PIF/dopamine) of the hypothalamus tonically </li></ul><ul><li>suppresses prolactin secretion </li></ul><ul><li>TRH (thyrotopin-releasing hormone) prolactin secretion </li></ul><ul><li>Estrogenes prolactin synthesis and release </li></ul><ul><li>Stimulation of the nipple during breast feeding/nursing, leads to prolactin release </li></ul>
  14. 19. Clinical <ul><li>Excessive secretion of prolactin ( hyperprolactinemia ), is a common disorder in </li></ul><ul><li>humans due to microadenoma of the prolactin secreting cells </li></ul><ul><li>Common manifestations of hyperprolactinemia: </li></ul><ul><li>in women: </li></ul><ul><li>- lack of menstrual cycle </li></ul><ul><li>- galactorrhea (excessive & spontaneous secretion of milk) </li></ul><ul><li>in men: </li></ul><ul><li>- hypogonadism - breast enlargement (gynecomastia) </li></ul><ul><li>- decreased sex drive - rarely galactorrhea </li></ul><ul><li>- low sperm count </li></ul>
  15. 20. Antidiuretic hormone (ADH)/Vasopressin (AVP) <ul><li>ADH is a nanopeptide, secreted mainly by the supraoptic nuclei of the </li></ul><ul><li>hypothalamus and released from the posterior pituitary (its carrier protein, </li></ul><ul><li>neurophysin is also released) </li></ul><ul><li>ADH conserves body water by reducing the volume of urine ( antidiuresis ) </li></ul><ul><li>It acts primarily on the collecting tubules of the kidney, forms “ water channels ” and </li></ul><ul><li>promotes reabsorption of water from the glomerular filtrate back into the circulation </li></ul><ul><li>Reabsorption of this “ solute-free ” water plasma osmolarity and increase osmo- </li></ul><ul><li>larity of urine </li></ul><ul><li>ADH/vasopressin widespread vasoconstriction arterial pressure </li></ul><ul><li>Osmoreceptors in the hypothalamus sense plasma osmolarity </li></ul><ul><li>plasma osmolarity ( normal ~ 290 mOsm/L ) ADH secretion </li></ul><ul><li>ADH H 2 O conservation by kidney H 2 O balance </li></ul>
  16. 21. <ul><li>osmolarity of plasma thirst sensation ( center in the hypothalamus ) drinking </li></ul><ul><li>H 2 O balance </li></ul><ul><li>Decrease in ECF/blood volume volume receptors (in atria) monitor </li></ul><ul><li>ADH secretion </li></ul><ul><li>Nausea & vomiting ADH secretion </li></ul>
  17. 22. Clinical <ul><li>Diabetes insipidus (excessive loss of body H2O in urine) </li></ul><ul><li>Types: </li></ul><ul><li>- Neurogenic (hypothalamic/central) </li></ul><ul><li>- deficiency in secretion of ADH from the posterior pituitary (due to trauma, </li></ul><ul><li>infections or tumors) </li></ul><ul><li>- Nephrogenic (due to ADH receptor deficiency in kidney) </li></ul><ul><li>Diabetes insipidus urine production (10-16 L/day). However, the loss is </li></ul><ul><li>compensated by water intake. </li></ul>
  18. 23. Oxytocin <ul><li>Oxytocin is a nine amino acid peptide , synthesized mainly by paraventricular </li></ul><ul><li>nuclei in the hypothalamus and transported down the axons to the posterior </li></ul><ul><li>pituitary for secretion into blood </li></ul><ul><li>It is also formed in the ovaries and testes </li></ul><ul><li>Oxytocin stimulates contraction of myoepithelial cells of mammary gland alveoli, </li></ul><ul><li>causing milk ejection ( milk letdown ) </li></ul><ul><li>Oxytocin is involved in facilitating sperm transport both in the females and in the </li></ul><ul><li>males genital tracts </li></ul><ul><li>Oxytocin is released during labor </li></ul><ul><li>- fetus stimulates the cervix & vagina stretch reflex oxytocin </li></ul><ul><li>secretion prostaglandins contraction of uterine smooth </li></ul><ul><li>muscle parturition ( birth ) </li></ul><ul><li>Physical stimulation of nipples/teats initiates oxytocin release (a neurohormonal </li></ul><ul><li>reflex ) </li></ul><ul><li>In males, oxytocin is released in pulses during ejaculation </li></ul><ul><li>Acute stress oxytocin secretion </li></ul><ul><li>Estrogen oxytocin receptor synthsis </li></ul><ul><li>Alcohol drink oxytocin secretion </li></ul>

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