2Hypothalamus 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.
3Hypothalamus 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
4Posterior 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.
5Anterior 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).
10Hypothalamic releasing factors for anterior pituitary hormones Travel to adenohypophysis via hypophyseal-portal circulationTravel to specific cells in anterior pituitary to stimulate synthesis and secretion of trophic hormones
11Hypothalamic releasing hormones Effect on pituitaryCorticotropin releasing hormone (CRH)Stimulates ACTH secretionThyrotropin releasing hormone (TRH)Stimulates TSH and Prolactin secretionGrowth hormone releasing hormone (GHRH)Stimulates GH secretionSomatostatinInhibits GH (and other hormone) secretionGonadotropin releasing hormone (GnRH)Stimulates LH and FSH secretionProlactin releasing hormone (PRH)Stimulates PRL secretionProlactin inhibiting hormone (dopamine)Inhibits PRL secretion
12Characteristics of hypothalamic releasing hormones Secretion in pulsesAct on specific membrane receptorsTransduce signals via second messengersStimulate release of stored pituitary hormonesStimulate synthesis of pituitary hormonesStimulates hyperplasia and hypertophy of target cellsRegulates its own receptor
13Anterior pituitaryAnterior 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).
17Feedback 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.
23Growth 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 intakeDuring 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.
24Growth hormone vs. metabolic state During fasting, GH antagonizes insulin action and helps mediate glucose sparing, ie stimulates gluconeogenesisIn 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
26ACTH: adrenocorticotropic hormone: synthesis and regulation of secrtion Produced in corticotrophsACTH 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
28ACTH ACTH is made up of 39 amino acids Regulates adrenal cortex and synthesis of adrenocorticosteroidsa-MSH resides in first 13 AA of ACTHa-MSH stimulates melanocytes and can darken skinOverproduction of ACTH may accompany increased pigmentation due to a-MSH.
29Addison’s DiseaseDisease in which patients lack cortisol from zona fasiculata, and thus lacks negative feedback that suppresses ACTH productionResult: overproduction of ACTHSkin color will darkenJFK had Addison’s disease and was treated with cortisol injections
30b-endorphin Produced as a result of ACTH synthesis Binds to opiate receptorsResults in “runner’s high”Role in anterior pituitary not completely understoodOne of many endogenous opiods such as enkephalins
32Regulation of ACTH Stimulation of release CRH and ADHStressHypoglycemiaCRH and ADH both synthesized in hypothalamusADH is released by posertior pituitary and reaches anterior pituitary via inferior hypophyseal artery.
33ACTH Circadian pattern of release Highest levels of cortisol are in early AM following ACTH releaseDepends on sleep-wake cycle, jet-lag can result in alteration of patternOpposes the circadian pattern of growth hormone secretion
35ACTH Acts on adrenal cortex stimulates growth of cortex (trophic action)Stimulates steroid hormone synthesisLack of negative feedback from cortisol results in aberrantly high ACTH, elevated levels of other adrenal corticosteroids– adrenal androgensAdrenogenital syndrome: masculization of female fetus
36Glycoprotein hormones LH, FSH, TSH and hCGa and b subunitsEach subunit encoded by different genea subunit is identical for all hormonesb subunit are unique and provide biological specificity
37Glycoprotein hormones Glycoprotein hormones contain two subunits, a common a subunit and a distinct b subunit: TSH, LH, FSH and hCG.
38Gonadotrophs Cells in anterior pituitary that produce LH and FSH Synthesis and secretion stimulated by GnRH– major effect on LHFSH secretion controlled by inhibinPulsitile secretion of GnRH and inhibin cause distinct patterns of LH and FSH secretion
39LH/FSH Pulsatile pattern of secretion LH pulses are biphasic (every 1 minute, then large pulse at 1 hour)FSH pulses are uniphasicDiurnal– LH/FSH more pronounced during pubertyCyclic in females– ovarian cycle with LH surge at time of ovulationMales are not cyclic, but constant pulses of LH cause pulses of testosterone to be produced
41Regulation of LH/FSH Negative feed-back Inhibin produced by testes and ovaries Decreases FSH b-subunit expressionTestosterone from Leydig cells– synthesis stimulated by LH, feedsback to inhibit GnRH production from hypothalamus and down-regulates GnRH receptorsProgesterone– suppresses ovulation, basis for oral contraceptives. Works at both the level of pituitary and hypothalamus.
42Regulation of LH/FSHDopamine, endorphin, and prolactin inhibit GnRH release.Prolactin inhibition affords post-partum contraceptive effectOverproduction of prolactin via pituitary tumor can cause amenorrhea– shuts off GnRHTreated with bromocryptine (dopamine agonist)Surgical removal of pituitary tumor
43Regulation of LH/FSH Positive feedback Estradiol at high plasma concentrations in late follicular phase of ovarian cycle stimulates GnRH and LH surge– triggers ovulation
47Lacotrophs Site of production of prolactin Lactogenesis (milk synthesis) requires prolactinTonically inhibitedOf the anterior pituitary hormones, the only oneMultifactoral control, balance favors inhibitionDopamine inhibits prolactinProlactin releasing hormone is TRHOcytocin also stimulates prolactin releaseEstradiol enhances prolactin synthesis
48Prolactin Stimulates breast development and lactogenesis May be involved in development of Leydig cells in pre-pubertal malesImmunomodulatory effects– stimulates T cell functionsProlactin receptors in thymus
49Posterior pituitary hormones: ADH (AVP) and Oxytocin (really hypothalamic hormones) Both are synthesized in the cell bodies of hypothalamic neuronsADH: supraoptic nucleusOxytocin: paraventricular nucleusBoth 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
52Oxytocin: stimulates myoepithelial contractions In uterus during parturitionIn mammary gland during lactation
53Oxytocin: 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.
54Oxytocin: uterine contractions Reflexes originating in the cervical, vaginal and uterus stimulate oxytocin synthesis and release via neural input to hypothalamusIncreases in plasma at time of ovulation, parturition, and coitusEstrogen increases synthesis and lowers threshold for release
56ADH: conserve body water and regulate tonicity of body fluids Also known as vasopressinRegulated by osmotic and volume stimuliWater deprivation increases osmolality of plasma which activates hypothalmic osmoreceptors to stimulate ADH release