Physiology of the Hypothalamus and Pituitary Gland

they function in a coordinated fashion for the release of hormones (hypothalamic-pituitary unit)

How do the hypothalamus and pituitary gland interact?

-regulates thyroid, adrenal, and reproductive glands

-controls growth

-milk production

-milk ejection

-osmoregulation

What are the 5 main functions of the hypothalamic-pituitary unit?

-thermoregulation

-energy balance and hunger

-thirst and osmoregulation

-circadian rhythms

-reproduction

-stress response

-can influence sympathetic outflow (aka blood pressure regulation)

What are the 7 main set points contained within the hypothalamus?

generates and coordinates circadian rhythm by controlling melatonin levels

What is the function of the suprachiasmatic nucleus (SCN) of the hypothalamus?

hypothalamus and pituitary gland:

hypophysis

What is the pituitary gland also known as?

a posterior lobe and anterior lobe

What does the structure of the pituitary gland (hypophysis) consist of?

the neurohypophysis

What is the posterior lobe of the pituitary also called?

contains neurons that release neuropeptides (exocytosed bc peptides!)

What is the composition of the posterior lobe like?

the adenohypophysis

What is the anterior lobe of the pituitary also called?

hypothalamus is connected to pituitary gland by a thin stalk called the infundibulum (aka hypophysial stalk)

How do the hypothalamus and pituitary gland interact structurally?

damage due to trauma/cut can affect the release of hormones

What is the clinical significance of the infundibulum/hypophysial stalk?

controls the pituitary gland by both neural and hormonal mechanisms

How does the hypothalamus affect the pituitary gland?

neural tissue

What is the posterior pituitary lobe derived from?

-arginine vasopression (AVP)

-oxytocin

What 2 peptide hormones (neuropeptides) does the posterior pituitary lobe release?

it binds to 2 main receptors

How does AVP elicit its effects?

*vasopressin 1, V1 -> acts on blood vessels to vasoconstrict

*vasopressin 2, V2 -> acts on the kidneys to reabsorb water

What are the 2 main receptors that AVP binds, and explain?

in the supraoptic nucleus (SON)

Where is AVP located within the hypothalamus?

in the paraventricular nucleus (PVN)

Where is oxytocin located within the hypothalamus?

ribosomes and golgi -> to form the neuropeptides

What are the 2 main organelles in the nuclei of the hypothalamus, and explain?

microtubules go down the axon tract to carry the neuropeptides and take them to the dendrite

How do neuropeptides produced in the nuclei of the hypothalamus reach the posterior pituitary gland?

chemotherapy drugs that block microtubule synthesis can impact oxytocin and AVP neuropeptide release

What is the clinical significance of microtubule involvement in the release of neuropeptides from the hypothalamus to the posterior pituitary gland?

primarily a collection of endocrine cells that will secrete 6 peptide hormones

What is the composition and function of the anterior pituitary gland like?

*thyroid-stimulating hormone (TSH)

*follicle-stimulating hormone (FSH)

*luteinizing hormone (LH)

*growth hormone (GH)

*prolactin (PRL)

*adrenocorticotropic hormone (ACTH)

What are the 6 peptide hormones that the anterior pituitary gland will secrete?

they are linked directly by hypothalamic-hypophysial portal blood vessels

How do the hypothalamus and anterior pituitary interact?

provide most of the blood supply of the anterior lobe and allows the hypothalamus to directly control the anterior pituitary gland

What is the function of the hypothalamic-hypophysial portal blood vessels that link the hypothalamus and anterior pituitary?

the way hormones, tissues, and organ systems interact to influence each other's activity -> anterior pituitary hormones can increase blood glucose and the pancreas can release insulin in response

What is endocrine cross-talk, and explain?

anterior pituitary gland:

they are both long and short

What is the length of the portal vessels in the blood supply of the anterior pituitary?

they converge to form the long hypophysial portal vessels

What do capillary plexuses in the hypothalamus do?

they travel down the infundibulum to deliver venous blood to the anterior lobe of the pituitary

What happens to the long hypophysial portal vessels of the hypothalamus?

forms the inferior hypophysial arteries in the lower portion of the infundibular stem

What does a capillary plexus parallel to the long hypophysial portal vessels do?

the short hypophysial portal vessels

What is formed by the inferior hypophysial arteries (capillaries) in the lower portion of the infundibular stem?

most of the blood that supplies the anterior pituitary is venous blood

What is the unique feature regarding blood supply to the anterior pituitary?

-the hypothalamic hormones can be delivered to the anterior pituitary directly and in high concentration

-the hypothalamic hormones will not appear in the arterial circulation in high concentrations

What are the 2 important features of the anterior pituitary blood supply?

cannot sample blood from there! -> would have to stimulation test by giving body TRH and then look to see if TSH if produced by pituitary gland

How can hormone levels in the hypothalamic-hypophysial portal vessels tested, and explain?

note the 2 sets of portal vessels at the anterior pituitary!

-somatotrophs -> GH

-corticotrophs -> ACTH

-thyrotrophs -> TSH

-gonadotrophs -> FSH, LH

-lactotrophs -> prolactin (PRL)

What are the 5 cell types of the anterior pituitary, and the hormone released by each?

somatotrophs (30-40% of cells) and corticotrophs (20%) -> all other cell types make up 5-15% of cells

What are the 2 most prevalent cell types in the anterior pituitary, and explain?

anterior pituitary hormones:

releasing and inhibitory hormones control the secretion of specific hormones

How is the function of the anterior pituitary controlled?

in a pulsatile manner (due to sleep, exercise, meal ingestion, etc)

How are the releasing and inhibitory hormones that control the secretion of specific hormones from the anterior pituitary gland released?

some portions of the hypothalamus are not protected by the BBB

What is the protection of the hypothalamus like?

allows for establishment of hormonal feedback loops

What is the function of the unprotected hypothalamus?

PTH, insulin, glucagon, and calcitriol are not controlled by the hypothalamus

How does the hypothalamus control PTH, insulin, glucagon, and calcitriol?

-releasing hypothalamic hormones

-inhibitory hypothalamic hormones

What are the 2 main types of hormones released by the hypothalamus?

dopamine

What is prolactin-inhibiting hormone (PIH), produced by the hypothalamus?

if a patient is taking a dopamine antagonist drug, it will cause the release of prolactin due to the loss of inhibition -> this can increase breast tissue (gynecomastia) and lead to infertility

What is the pharmacological significance of dopamine being a prolactin-inhibiting hormone, and explain?

somatostatin

What is growth hormone inhibitory hormone (GHIH), produced by the hypothalamus?

hypothalamic releasing and inhibitory hormones:

it is a highly vascularized tissue!

What is the vascularization of the anterior pituitary like?

the hypothalamus communicates with the anterior hypophysis via vasculature

What is the functional significance of the anterior pituitary being a highly vascularized tissue?

they are fenestrated; allowing for easy passage of releasing or inhibitory hormones

What is the structure of the portal vessels of the hypothalamus like, and explain?

occurs by diffusion

How does the flow of hormones into or out of portal systems occur?

concentration gradients

(bc it occurs by diffusion!)

What is the rate of the flow of hormones into or out of portal systems governed by?

AVP and oxytocin

What are the hormones secreted by the posterior pituitary?

neuropeptides

What class of hormones are AVP and oxytocin?

synthesized in the neuron cell bodies in the hypothalamus from larger precursor molecules

How are the neuropeptides AVP and oxytocin synthesized?

-prepropressophysin

-preprooxyphysin

What are the 2 larger precursor molecules from which the neuropeptides AVP and oxytocin are synthesized?

in the supraoptic nuclei (SON)

Where in the hypothalamus is AVP primarily formed?

in the paraventricular nuclei (PVN)

Where in the hypothalamus is oxytocin primarily formed?

carrier proteins that assist in the axonal transport of AVP and oxytocin to the axon terminals in the posterior pituitary gland

What are neurophysins?

released as well during exocytosis of vesicles

When are neurophysin proteins released?

controls the rate of water excretion into the urine (via V2 receptor) and increases vasoconstriction (via V1 receptor)

What is the function of AVP from the posterior pituitary?

helps with milk let down from the mammary glands of the breast

What is the function of oxytocin from the posterior pituitary?

during suckling and also helps in uterine smooth muscle contraction during child delivery

When is oxytocin released?

positive feedback

What type of feedback is involved in oxytocin release?

posterior pituitary:

-increased plasma osmolarity

-decreased blood volume

-decreased blood pressure

-drugs or tumor (SIADH)

As a result of what 4 things is the release of AVP increased?

into systemic circulation

Where is AVP released to?

it can bind to either V1 receptors on blood vessels or V2 receptors on kidneys

What happens when AVP is released into systemic circulation?

by stimulation of the anteroventral region of the 3rd ventricle (AV3V)

What is another way that secretion of AVP can be induced?

by angiotensin II (AngII)

How is the anteroventral region of the 3rd ventricle (AV3V) stimulated, and explain?

increases AVP release, thirst, and sodium appetite

What happens when the anteroventral region of the 3rd ventricle (AV3V) is stimulated by angiotensin II (AngII)?

in the vicinity of the AV3V and SON

Where are osmoreceptors located?

AVP release increased due to increased plasma osmolarity:

alpha 2 adrenergic antagonists can cause increased release and inappropriate release of ADH because negative feedback is abolished -> elevates BP

How do alpha 2 adrenergic antagonist drugs affect ADH?

via negative feedback loops and osmoreceptors

How can the level of AVP activation at the level of the hypothalamus be controlled?

plasma osmolarity

What are osmoreceptors sensitive to?

AVP secretion can occur with only 1-2 mOsm increase and maximum AVP secretion occurs at 395 mOsm/L

When can AVP secretion occur, considering plasma osmolarity?

ADH levels are abnormally high -> due to excessive secretion from posterior pituitary or from abnormal sites (lung tumor)

What happens to ADH levels in syndrome of inappropriate antidiuretic hormone secretion (SIADH), and explain?

inhibition is lost

What is feedback like in SIADH?

-increased serum osmolarity

-decreased ECF volume

-angiotensin II

-pain

-nausea

-hypoglycemia

-nicotine

-opiates

-antineoplastic drugs

What are 9 stimulatory factors of ADH secretion?

-decreased serum osmolarity

-ethanol

-alpha adrenergic agonists

-atrial natriuretic peptide

What are 4 inhibitory factors of ADH secretion?

negative feedback loops can control the level of AVP activation at the level of the hypothalamus:

-central diabetes insipidus

-nephrogenic diabetes insipidus

What 2 conditions can the absence of AVP be?

a failure to release AVP at the pituitary gland

What is central diabetes insipidus?

decreased response to AVP in the kidney

What is nephrogenic diabetes insipidus?

dilute urine and hyperosmotic plasma

What is the plasma and urine like in DI?

a AVP analog called desmopressin (DDAVP)

What pharmacological therapy can central DI patients be given?

women who are pregnant can develop gestational DI during the 3rd trimester

What is the relevance of diabetes to pregnant patients?

due to placental vasopressinase and is transient (rare event)

Why can women who are pregnant develop gestational DI during the 3rd trimester?

DI patients can become dehydrated and have higher incidence of xerostomia increasing caries risk

What is the dental significance of DI?

the absence of AVP can be central DI or nephrogenic DI:

a variety of hormonal stimuli -> including estrogen, progesterone, prolactin, oxytocin, thyroid hormone, cortisol, and growth hormone

What are breast development and function initiated by, and explain?

is the primary stimulus for lactogenesis in late pregnancy and the postpartum period

What is the function of prolactin?

-smooth muscle contraction

-bonding behavior

Generally, what are the 2 main functions that oxytocin stimulates?

through G-alpha-q-dependent pathway (GPCR) to increase intracellular Ca2+

How does oxytocin induce smooth muscle contraction?

-stimulates uterine contractions during parturition

-stimulates milk letdown and ejection from the lactating breast

-promotes maternal and social bonding behavior

Specifically, what are the 3 main functions of oxytocin?

there are oxytocin agonists drugs used for labor induction and as a uterotonic to decrease post-partum hemorrhage (ex: Pitocin)

How can pharmacotherapeutics utilize the functions of oxytocin?