Hypothalamic/Pituitary Flashcards
How are hormones released from hormone secreting cells into circulation?
Hormones are released into the interstitial connective tissue and then pass directly into blood or lymph circulation. endocrine cells, tissues, glands, and organs are called ductless
Cells are usually arranged how in endocrine glands?
into cords and clumps and are surrounded by an extensive capillary network that allows for more efficient transport of hormones
What is the make up of Adenohypophysis? What is it derived from?
glandular epithelium; ectoderm
What is the make up of neurohypophysis? What is it derived from?
neural secretory tissue; neuroectoderm
Epithelial portion of pituitary gland develops from what?
pharyngeal roof and Rathke’s pouch, Pouch detaches and becomes the cellular portion, anterior pituitary
What forms the neural portion/posterior pituitary?
Down growth of brain ; Neurohypophysis remains attached to hypothalamus by a neural stalk, infundibulum
What is the histological appearance of the posterior pituitary lobe?
less cellular, appears to have streaks & is directly attached to the hypothalamus
What is the histological appearance of the anterior pituitary lobe?
glandular, densely packed cells & not directly attached to the hypothalamus
What are the derivatives from Rathke’s pouch?
Pars distalis, pars Intermedia, pars tuberalis
Where is the pars distalis?
comprises the bulk & arises from the thickened anterior wall of the pouch
Where is the pars Intermedia?
thin remnant of the posterior wall of the pouch that abuts the pars distalis
Where is the pars tuberalis?
forms a collar or sheath around the infundibulum and developed from the thickened lateral wall
What is the make up of the pars distalis?
bulk of the anterior pituitary gland (75%) , cords of well-stained endocrine cells interspersed with fenestrated capillaries & supporting reticular connective tissue
What are the three cell types in the pars distalis based on staining?
acidophils, basophils, chromophobes
What are the staining characteristics of acidophils?
large cells that stain deeply eosinophilic & appear red in Mallory stain (40%)
What are the staining characteristics of basophils?
appear blue/purple in Mallory stain (10%)
What are the staining characteristics of chromophobes?
stain weakly with few or no secretory granules; represent a heterogeneous group of cells including stem cells, undifferentiated progenitors & degranulated cells (50%)
What are the types of acidophils?
somatotrophs and lactotropes (mammotropes)
What do somatotrophs secrete? what stimulates them? inhibits them? general effect?
secrete somatotropin (growth hormone), stimulated by GHRH, inhibited by somatostatin, general effect of increasing metabolic rates, induces the liver to produce insulin-like growth factor-a (IGF-1) which stimulate bone and muscle growth
What do lactotropes secrete? what stimulates them? inhibits them? general effect?
secrete prolactin, stimulated by PRH and oxytocin, inhibited by dopamine/PIF, promotes mammary gland development and lactation, the number of mammotrophs increases following birth, and drop after nursing stops.
What are the types of basophils?
gonadotrophs, thyrotrophs, corticotrophs
What do corticotrophs secrete? what stimulates them? inhibits them? general effect?
secrete precursor to adrenocorticotropic hormone (ACTH), stimulated by CRH (corticotropin releasing hormone), inhibited by high plasma cortisol levels, stimulates synthesis and release of hormones from the adrenal cortex
What do thyrotrophs secrete? what stimulates them? inhibits them? general effect?
secrete thyrotropin (thyroid-stimulating hormone), stimulated by TRH, inhibited by thyroxine (T4) and triiodothyronine (T3) in the blood, stimulates synthesis and release of thyroid hormones
What do gonadotrophs secrete? what stimulates them? inhibits them? general effect?
secrete follicle stimulating hormone (FSH) and luteinizing hormone (LH), stimulated by GnRH, inhibited by hormones produced by ovaries and testes, stimulates ovarian follicle growth and estrogen secretion, steroid hormone production in the testes.
What is the make-up of the pars Intermedia?
contains cuboidal follicular cells and colloid cysts called Rathke cysts, which are lined by follicular cells
What are rathke cysts derived from? What are they?
ectoderm of the dorsal portion of the Rathke pouch; thought to be remnants of rathke pouch
What do the secretory cells in the pars Intermedia produce and secrete?
melanocyte-stimulating hormone (MSH)
What is the make up of the pars tuberalis?
parenchymal cells arranged in small clusters/cords associated with blood vessels, nests of squamous cells & small follicles lined with cuboidal cells arranged in cords which show immunoreactivity to ACTH, FSH, and LH, highly vascular area containing veins of the hypothalamohypophyseal system
What is a pituitary adenoma?
Benign tumors of the anterior pituitary gland, Can be classified with immunocytochemistry targeted to specific hormones, Primary tumors can compress the hypothalamus, cranial nerves or the optic chiasm
What is the hypothalamic-hypophyseal tract?
consists of axons extending from the hypothalamic supraoptic and paraventricular nuclei, through the infundibulum and into the pars nervosa of the posterior pituitary, where peptide hormones they carry are released for capillary uptake
What is unique about the neurohypophysis?
NOT an endocrine gland; it’s a storage site for neurosecretions from the hypothalamus, direct neural connection to hypothalamus via multitude of unique unmyelinated axons, do not terminate on other neurons; instead end in close proximity to fenestrated capillaries of the pars nervosa, contain secretory vessels & have well developed Nissl bodies
What are Nissl bodies?
large basophilic bodies of nerve cells that contain rER & large #s of free ribosomes
What is the make-up of the infundibulum?
continuous with the median eminence and contains the neurosecretory axons forming the hypothalamohyophyseal tracts
What are herring bodies?
Accumulations of secretory granules are evident as distentions of the axons; contain membrane-bound granules of antidiuretic hormone (vasopressin) or oxytocin
What are pituicytes?
neuroglial cells that surround and support the axons extending from the hypothalamus, Most abundant cell in pars nervosa, In contact with axons & capillaries, Serve a supporting role similar to astrocytes in the CNS
What hormones are secreted from the neurohypophysis?
ADH and oxytocin
What does ADH do?
modulates the plasma membrane permeability of the kidney, conserves water by increasing resorption of water in the kidneys, effect of lowering urine volume but increasing its concentration
What does oxytocin do?
stimulates smooth muscle contraction of the uterus during orgasm, menstruation, and labor; stimulates contractions of myoepithelial cells of mammary glands, assisting in milk ejection
What supplies the primary capillary plexus? Where does it drain?
receives blood from the superior hypophyseal arteries, drains blood into the hypophyseal portal veins supplying the secondary capillary plexus
What supplies the secondary capillary plexus and where does it drain? What does it do?
primary capillary plexus ,drains into the hypophyseal veins, ) carries neurosecretory hormones from the median eminence into the pars distalis where they stimulate or inhibit basophils and acidophils to produce hormones.
The pars nervosa receives blood mainly from where?
inferior hypophyseal arteries, arise from the internal carotid artery and the trabecular artery (arises from superior hypophyseal artery)
The hormones released by Herring bodies enter the blood circulation through what?
capillary plexuses of the inferior hypophyseal and trabecular arteries.
What is the utility of hypothalamic hypophyseal portal system?
allows minute quantities of hypothalamic hormones to be carried in concentrated from directly to the target cells in anterior pituitary, hormones are not diluted out in the systemic circulation
What are the different types of neurohormonal or neurosecretory cells?
magnicellular, paravicellular hypophysiotropic neurons, and hypothalamic projection neuron
What is the set up of magnicellular neurons?
body located in the hypothalamus, processes projected into neurohypophysis; neurohromone released into circulation from nerve endings
What is the set up of parvicellular hypophysiotropic neurons?
cell body located in hypothalamus, processes release neurohormones into hypophysial portal system to regulate the anterior pituitary hormone release
What is the set up of the hypothalamic projection neuron?
cell body in hypothalamus, neuronal processes terminate at chemical synapses on other neurons
What are the different hypothalamic nuclei?
SON, PVH, INF (infundibular), ARC (arcuate), POST (posterior), PeVH (periventricular)
What three factors determine the physiological effects of hormones determined mainly by their concentration in the blood?
rate of production (regulated by positive and negative feedback circuits), rate of delivery (high blood flow delivers more hormone than low flow, and rate of degradation and elimination or half-life
What are the different endocrine rhythms?
circadian, ultradian, infradian, diurnal, and nocturnal
What is the purpose of the hierarchical system to the endocrine system?
an amplifying cascade
What are the aspects of ADH production?
synthesized as a prohormone, stored in secretory vesicles after removal of signal sequence, prohormone stored in vesicles has: ADH, neurophysin and glycopeptide; cleavage occurs at time of release and exocytosis of vesicles
Where is ADH degraded?
liver and kidney; 18 minutes half life
What regulates ADH secretion?
plasma osmolality (sensed by osmoreceptors in OVLT), activation of osmoreceptors stimulates ADH secretion; also stimulated by a decrease in BP and volume, sensed by stretch receptors in heart and large arteries signal sent to NTS
What happens when ADH activates the V1 receptor?
vasoactive effects in vascular smooth mucle cells; signaling initiated by activation of phospholipase C, DAG, PKC, and IP3 path
What happens when ADH activates the V2 receptor?
renal effects; activation of andenylate cyclase, generation of cAMP, and PKA activation
What effects does ADH have on the kidney?
stimulates water reabsorption by stimulating insertion of aquaporin 2 only; 3 & 4 are constitutively expressed
What are the 2 types of diabetes Insipidus?
hypothalamic- central, deficiency of ADH secretion from posterior pit. caused by trauma, infections, or tumors of hypothalamus, treat with exogenous ADH; or nephrogenic- normal ADH but no response, kidneys fail to respond due to renal disease, mutations in ADH receptor gene, mutation in gene encoding aquaporin 2
What are the aspects of oxytocin synthesis?
synthesized in hypothalamic magnicellular neurons of PVH and SON; packaged into granules and secreted along carrier protein called neurophysin II
What does oxytocin do?
stimulation of milk ejection into ducts through contraction of myoepithelial cells of alveoli and stimulation of uterine smooth muscle contraction at birth
How does oxytocin signal in the cell?
via Gq, activating phospholipase C, DAG, PKC, and IP3
What things negatively feedback on pituitary effecting oxytocin release?
stress, depression, and catecholamines
What things positively feedback on pituitary effecting oxytocin release?
suckling stimulus on alveolus, myometrial contraction during labor
Stimulation of nipples produce a neurohormonal reflex stimulates oxytocin release how?
NT/neuropeptides activated by different inputs to stimulate or inhibit magnicellular neurons to produce synchronous and pulsatile depolarization of oxytocinergic magnicellular neurons in SON and PVH
What is the fergusen reflex?
at parturition, contraction is mediated by uterine smooth muscle cells that have oxytocin receptors, primary stimulus for maternal release appears to be distension of the cervix
How do sex steroids effect oxytocin release?
estrogen increases the number of receptors in uterine myometrium of pregnant women late in gestation and up to 200-fold just prior to labor; decline in progesterone facilitates burst of oxytocin release at birth
What causes abnormalities in the hypothalamus?
developmental or acquired due to trauma or other factors
In adults what is the most common cause of hypothalamic and pituitary dysfunction?
pituitary adenoma; headache and visual loss
In children what is the most common cause of hypothalamic and pituitary dysfunction?
craniopharyngiomas and other hypothalamic tumors are the main cause for hypothalamic-pituitary dysfunction
What is CRH do and when is it secreted?
secreted in response to stress (pain, trauma, hypoxia, acute hypoglycemia, cold exposure, depression); stimulates ACTH production from pituitary corticotrophs and corticotropes
What does ACTH do?
stimulates the adrenal cortex (zona fasciculate/reticularis) to secrete cortisol
What inhibits ACTH?
high circulating levels of cortisol
What inhibits the release of CRH?
high circulating levels of cortisol and high ACTH levels
How is ACTH release augmented by ADH and angiotensin II?
CRH receptor is a Gs increasing cAMP, ADH signals by PKC through Gq, elevated intracellular cAMP open L-type Ca channels and permit entry from outside, activation of PKC-mediated path causing release of Ca from ER; higher Ca cause exocytosis of vesicles containing ACTH which triggers cortisol production
What is the precursor of ACTH?
POMC (proopiomelanocortin which is cleaved into lipotropin, beta-endorphin and metenkephalin and MSH
How does ACTH stimulate cortisol?
binds to Gs in zona fasiculata/reticularis and elevates intracellular cAMP; signaling cascade inititates synthesis and activation of enzymes required for biosynthesis and activation of enzymes required for biosynthesis of cortisol from cholesterol
What cells secrete PRL? What is the hormone important for?
pituitary lactotrophs as a pro-hormone, cleaved into active hormone, also synthesized in other tissues; mammogenesis, lactogenesis, and galactopoiesis
What is mamogenesis?
mammary gland growth and development stimulated primarily by estrogens and progesterone in coordination with prolactin and human placental lactogen
What is lactogenesis?
initiation of lactation triggered by PRL acting on developed mammary gland (due to estrogen and progesterone), it is inhibited by high levels of estrogen and progesterone during pregnancy, which decline at birth
What is galactopoiesis?
maintainence of milk production requires both prolactin and oxytocin
What stimulates prolactin production?
TRH, TRH secreting neurons are located in PVN and PeVH
What inhibits PRL secretion?
dopamine; dopamine secretion is stimulated by prolactin to inhibit its own production; via Gi
How does suckling mammary gland development during nursing effect PRL secretion?
increases through dopamine inhibition; tactile receptors to hypothalamus to neurons in ARC, which increase PRL release and milk production
What is the primary regulatory method of prolactin secretion?
inhibition of dopamine rather than by stimulation through TRH
What affect does prolactin have on it’s own production?
binds to it’s own receptor on lactotrophs down-regulates its own mRNA levels/transcription
What is hyperprolactinemia?
excessive PRL secretion; caused by PRL-secreting tumors; in women causes ammenorhea and galactorrhea (excessive/spontaneous milk secretion); in men it causes hypogonadism, decreased sex drive, decreased sperm production and gynecomastia
What does deficiency in prolactin caused by and do?
destruction of anterior pituitary or lactotrophs, failure to lactate
What affect does prolactin have on GnRH, FSH, and LH?
inhibits ovulation by suppressing GnRH, and inhibits FSH and LH
Where is GnRH made? Where and how is it secreted?
hypothalamic neurons,, bind to gonadotrophs/gonadotropes; pulsatile information every 90-120 min
What does GnRH do? WHat inhibits it?
stimulates secretion of LH and FSH; high circulating sex steroids
What does LH do?
stimulates leydig cells to secrete testosterone, theca cells to secrete androstenedione, induces ovulation, promotes steroidogenessi in concert with FSH, required for maintainence of corpora luteum;
What does FSH do?
stimulates maturation of ovarian follicles, critical for sperm production/maturation by supporting function of sertoli cells,
what stimulates and what inhibits LH secretion?
stimulated by GnRH, inhibited by sex steroids circulating at high levels, and GnRH continuously or excessively (downregulated receptors)
what stimulates and inhibits FSH secretion?
stimulated by GnRH and activin secreted by gonadal, inhibited by sex steroids circulating at high levels, and GnRH continuously or excessively (downregulated receptors), also inhibin secreted by gonadal cells
What causes of low LH/FSH and how does it manifest?
results from hypogonadism, manifests as failure to produce normal sperm number and repro cycle cessation in females
What causes of high LH/FSH and how does it manifest?
usually reflects lack of steroid negative feedback; in general has no biological effect
Combined oral contraceptives are effective why?
inhibit LH surge required to induce ovulation
What does TRH do? where is it synthesized/secreted? What inhibits its secretion?
synth by neurons in PeVH and PVH of hypothalamus, stimulates TSH from pituitary thyrotrophs, inhibited by T3 & T4,
What does TSH do? where is it synthesized/secreted? What inhibits its secretion? stimulates?
stimulates T3 and T4 production, converted to T3 in peripheral tissues by deiodinase; synth and secreted by thyrotrophs in pituitary, inhibited by high T3 and T4, dopamine, and SS; stimulated by TRH (pulsatile, every 1.8h, peak between 12-4,
What cells secrete growth hormone?
somatotrophs
What does GH do? How?
controls growth and metabolism; directly on adipose tissues and liver, and indirectly mediated via IGF-1 secreted from the liver and peripheral tissues upon GH binding
What stimulates GH secretion? inhibits?
GHRH; SS, high IGF-1 levels via somatotrophs and stimulation of SS release from hypothalamus
What activities or conditions increase GH secretion? Decrease?
sleep, exercise, stress, hypoglycemia; elevated FA, glucocorticoids, hypothyroidism an hyperthyroidism
Disorders of the hypothalamus and pituitary typically result in what hormone being overproduced? What is it associated with?
PRL, associated with gonadal dysfunction; overproduction of TSH, FSH and LH are rare
In adults what is the most common disorder of the pituitary?
Pituitary adenoma, majority are hypersecreting, headache, visual loss, detected late
In adults what is the most common disorder of the pituitary/hypothalamus? How do they manifest?
craniopharyngiomas and other hypothalamic tumors; hyposecretion or hypersecretion of GH resulting in delayed puberty or diabetes insipidus
