Hypothalamus and Pituitary

Hypothalamus and PituitaryThe 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.

Hypothalamus and PituitaryPituitary 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

Posterior Pituitary: neurohypophysisPosterior 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.

Anterior pituitary: adenohypophysisAnterior 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).

Hypothalamus and pituitarygland

Hypothalamus and pituitarygland

Regulation of Hypothalamus

Anatomical and functional organization

Hypothalamic 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

Hypothalamic releasing hormones

Characteristics of hypothalamic releasing hormonesSecretion 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

Anterior 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).

Anterior pituitary cells and hormones

Hypothalamus and anterior pituitary

Anterior pituitary hormones

Feedback regulation of hypothalmus/pituitaryA 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.

Hypothalamus-pituitary axis

Feedback control

Feedback control of thyroid function

Feedback and restoration of homeostasis

Feedback control of growth hormone

Growth hormone vs. metabolic stateWhen 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.

Growth hormone vs. metabolic stateDuring 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

Growth hormone and metabolic state

ACTH: adrenocorticotropic hormone: synthesis and regulation of secrtionProduced 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

ACTH synthesis

ACTHACTH is made up of 39 amino acidsRegulates 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.

Addisons 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 Addisons disease and was treated with cortisol injections

b-endorphinProduced as a result of ACTH synthesisBinds to opiate receptorsResults in runners high Role in anterior pituitary not completely understoodOne of many endogenous opiods such as enkephalins

Regulation of ACTH secretion

Regulation of ACTH Stimulation of releaseCRH and ADHStressHypoglycemiaCRH and ADH both synthesized in hypothalamusADH is released by posertior pituitary and reaches anterior pituitary via inferior hypophyseal artery.

ACTHCircadian pattern of releaseHighest 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

Regulation of ACTH

ACTHActs on adrenal cortexstimulates 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 androgensAdrenogenital syndrome: masculization of female fetus

Glycoprotein hormonesLH, 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

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

GonadotrophsCells in anterior pituitary that produce LH and FSHSynthesis and secretion stimulated by GnRH major effect on LHFSH secretion controlled by inhibin Pulsitile secretion of GnRH and inhibin cause distinct patterns of LH and FSH secretion

LH/FSHPulsatile pattern of secretionLH 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

Pulsitile secretion of GnRH and LH

Regulation of LH/FSHNegative feed-backInhibin 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 receptorsProgesterone suppresses ovulation, basis for oral contraceptives. Works at both the level of pituitary and hypothalamus.

Regulation 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

Regulation of LH/FSHPositive feedbackEstradiol at high plasma concentrations in late follicular phase of ovarian cycle stimulates GnRH and LH surge triggers ovulation

Regulation of gonadotropin secretion

ThyrotrophsSite of TSH synthesisPattern of secretion is relatively steadyTSH secretion stimulated by TRHFeedback control by T3 (thyroid hormone)

Feedback control of thyroid function

LacotrophsSite of production of prolactinLactogenesis (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

ProlactinStimulates breast development and lactogenesisMay be involved in development of Leydig cells in pre-pubertal malesImmunomodulatory effects stimulates T cell functionsProlactin receptors in thymus

Posterior 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

Hypothalamus and posterior pituitary

Structures of ADH and oxytocin

Oxytocin: stimulates myoepithelial contractionsIn uterus during parturitionIn mammary gland during lactation

Oxytocin: milk ejection from lactating mammary glandsuckling 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.

Oxytocin: uterine contractionsReflexes 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

Oxytocin secretion is stimulated by nursing

ADH: 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

Regulation of ADH secretion

ADH increases renal tubular absorption of water

ADH and plasma osmolality

ADH and blood pressure