Endocrinology, Anterior Pituitary and Hypothalamus

linear growth; growth; cellular AA; lipolysis; glucose; glycogen; gluconeogenesis

Actions of GH: Promotes ________ ________ of bone (particularly long bones) by stimulating the growth and calcification of the epiphyseal plate. Hits cartilage plates, those stimulate rapid growth. Influences the _______ of the visceral organs, adipose and connective tissue, endocrine glands and striated muscle. Increases ___________ ____ uptake from the blood and stimulates DNA, RNA, protein synthesis (particularly in skeletal muscle and liver). Also big effect in connective tissue, tendons, ligaments, cartilage. Stimulation of ____________ within adipose tissue, and consequent increase in plasma free fatty acid levels, which encourages the use of fats for fuel. Decrease the rate of ___________ uptake and metabolism. Helps maintain blood glucose for the brain Increase ____________ breakdown and release of glucose to the blood. Increase *____________________ (glucose output) within the liver to maintain BG levels

uterine contraction, milk ejection

Actions of oxytocin:

ADH; oxytocin; posterior; releasing; inhibiting

Acts as the helmsman of the endocrine system in two important ways: Neurons within the supraoptic and paraventricular nuclei of the hypothalamus produce vasopressin (______) and _____________, which are transported down the axons and released from the ___________ pituitary to affect water balance and uterine contractility / breast milk ejection. Other neurons secrete ____________ or _____________ hormones into the blood, which influence the secretion of trophic hormones by the anterior pituitary gland.

GH

After puberty, when linear growth is complete and can no longer be influenced, excess levels of ______ cause increased periosteal bone growth, increased organ size, increased hand and foot size, enlargement of the tongue, coarsening of facial features, insulin resistance, and glucose intolerance.

pituitary gland

Also known as hypophysis (to grow under) 2 lobed organ (1 cm in diameter), size and shape of a pea -Anterior lobe - 75% of the pituitary mass -Posterior lobe

releasing

Although many different releasing and inhibiting hormones pass from the hypothalamus to the anterior lobe, the individual anterior pituitary target cells distinguish the messages directed to them and respond in kind - synthesizing and secreting the hormones, and shutting off hormone release in response to inhibiting hormones. The ___________ hormones are far more important as regulatory factors because very little hormone is stored by the secretory cells of the anterior lobe.

estrogen; progesterone

Although prolactin levels are very high during pregnancy, lactation does not occur because the high levels of __________ and _________________ downregulate prolactin receptors in the breast and block the action of prolactin. At parturition, these levels drop precipitously, and their inhibitory actions cease. Prolactin can then stimulate lactogenesis, and lactation can occur.

capillary plexuses; hypophyseal portal veins

Anterior pituitary: Made up of the primary and secondary ___________ __________ and the intervening ______________ ________ _______. The primary capillary plexus in the infundibulum communicates inferiorly via the small hypophyseal portal veins with a secondary capillary plexus in the anterior lobe.

TSH; FSH; LH; GH; prolactin; ACTH

Anterior pituitary: Formed from the epithelial tissue Primarily a collection of endocrine cells. Secretes six peptide hormones: _________, ______, _____, _____, ________, _______ The hypothalamus and anterior pituitary are linked directly by the Hypothalamic-Hypophyseal Portal System

releasing; inhibiting; secretory activity

Anterior pituitary: Via this system, ___________ and ____________ hormones secreted by neurons in the ventral hypothalamus circulate directly to the anterior pituitary, where they regulate the ___________ ____________ of its hormone-producing cells.

Na+

Control of ADH release is mainly due to changes in serum ____ level. A relative small increase in osmolarity (1-2%) increases the release of ADH so that less water is cleared and vice versa.

visceral control center

Despite its small size, the hypothalamus is the main ________ _________ ________ of the body.

deficiency; insensitivity

Diabetes insipidus: -Neurogenic -- ADH _______________ -Nephrogenic -- ADH __________________

GH

Dwarfism can be treated except in the case of a lack of (or damaged) receptors (rare); giving more ___ to someone without receptors would be counterproductive and end up having negative effects.

GH

Dwarfism may be treated with human ___ replacement

inhibitory

Excess prolactin can exert powerful _______________ effects on both male and female gonadal function and libido (sexual drive), primarily via actions on the CNS and by suppression of GnRH release.

acromegaly

Facial changes - thickening of the calvarium (skull), increased size of sinuses, enlargement of the nose and prognathism (jaw protrusion); increased soft tissue bulk and blunt fingers in hands

hypothalamic-hypophyseal portal system

Formed from the epithelial tissue Primarily a collection of endocrine cells. Secretes six peptide hormones: Thyroid-stimulating hormone (TSH) Follicle-stimulating hormone (FSH) Lutenizing hormone (LH) Growth hormone Prolactin Adrenocorticotropic hormone (ACTH) The hypothalamus and anterior pituitary are linked directly by the.........

trophic

Four of the six AP hormones are called ________ hormones, because they turn on endocrine glands or support the functions of other organs

TSH, ACTH, FSH, LH

Four of the six hormones of the anterior pituitary are called trophic hormones: _____, _______, ______, ____

insulin; diabetogenic

GH antagonizes the peripheral action ___________ (increases blood glucose levels) and is therefore generally considered to be a ___________________ hormone, in people who are not active or consuming large amounts of sugar.

childhood; puberty

GH levels are at their highest during early _______________ and particularly at ____________, then levels steadily decline throughout life.

TSH, FSH, LH family

Glycoproteins with sugar moieties covalently linked to asparagine residues in their polypeptide chains.

water; water loss

High osmolarity: ADH preserves _________ Low osmolarity: ADH is not released, causing ________ _______

acromegaly; gigantism

Hypersecretion of GH causes ______________ and/or ____________, Most often due to a growth hormone-secreting pituitary adenoma.

ADH

Hypersecretion of ______ is seen in children with meningitis, may follow neurosurgery or head injury, or be the consequence of ectopic ADH secretion by cancer cells, or hypovolemia. Marked by overretention of fluid, headache, and disorientation due to brain edema, weight gain, and hypoosmolarity of the blood.

GHRH; anterior pituitary; somatomedins; target tissues

Hyposecretion of GH: Include defects at every step in the hypothalamic-anterior pituitary-target tissue axis: Decreased secretion of ________ due to hypothalamic dysfunction Primary deficiencies of growth hormone secretion from the __________ ____________ Failure to generate ________________ (IGFs) in the liver Deficiency of GH or somatomedin receptors in ________ _________ (growth hormone resistance).

anterior; lactotrophs

Hyposecretion of prolactin: Can be caused either by destruction of the entire ____________ lobe of the pituitary or by selective destruction of the ______________. Leads to failure of lactation

diencephalon; thalamus; third ventricle

Hypothalamus: -Situated in part of the forebrain known as the _______________. Lies below the ____________ and forms the inferolateral walls of the ________ ______________

endocrine system

Hypothalamus: Performs many vital functions including: Autonomic control center Center for emotional response and behavior Body temperature regulation Regulation of food intake Regulation of water balance and thirst Regulation of sleep-wake cycles Control of ___________ ________ functioning

ADH secretion

Hypovolemia, ADH secretion: Could be due to hemorrhage Decreases in extracellular fluid volume of 10% or more cause a decrease in arterial blood pressure that is sensed by baroreceptors in the left atrium, carotid artery, and aortic arch. This information is transmitted via the vagus nerve to the hypothalamus, which directs an increase in ____ __________.

prolactin

If thyrotrophin releasing hormone is released, you will almost always get ______________ in addition to TSH

TRH

If you have a high concentration of Dopamine released, this will inhibit prolactin-inhibiting hormone, but not _____

gamete; gonadal hormones

In both sexes, FSH more stimulates __________ (sperm or egg) production, while LH more promotes production of __________ ___________. They work together.

hyposecretion of GH

In childhood, this leads to impairment of growth (dwarfism), characterized by a short statue, obesity and hypoglycemia.

secretion; osmolality

In contrast to diabetes insipidus, ADH levels are elevated due to stimulation of __________ by the increased _____________. Treated with thiazide diuretics, which interfere with dilution of the urine.

LH surge; ovulation; estrogen; progesterone

In females (mid-cycle), LH works with FSH (___ ________) to cause maturation of an egg-containing ovarian follicle. It then independently triggers the _______________ (expulsion of egg from follicle) and promotes synthesis and release of ovarian hormones (_____________ and _________________).

fertility

In females, prolactin inhibits ovulation by inhibiting the synthesis and release of gonadotropin-releasing hormone (GnRH). This will decrease ___________ in nursing mothers during breast-feeding

infertility

In males with high prolactin levels (e.g. due to prolactinoma), there is a parallel inhibitory effect on GnRH secretion and spermatogenesis, resulting in _____________.

testosterone; spermatogenesis

In males, LH stimulates the interstitial cells (Leydig) of the testes to produce the male hormone _________________. It also stimulates ________________________.

ADH; water; urine

In neurogenic diabetes insipidus, circulating _____ is low, the distal collecting ducts are impermeable to ______, and the ______ cannot be concentrated.

dopamine; estrogen

In persons who are not pregnant or lactating, prolactin secretion is tonically inhibited by _______________ (prolactin-inhibiting hormone) released from the hypothalamus. Release is promoted by various substances including TRH, and various stressors like fear, hypoglycemia, or anaesthesia / surgery. In females, prolactin levels rise and fall in rhythm with _____________ blood levels.

gigantism

In young patients, excessive levels of GH causes ____________ (increased linear growth). Due to intense hormonal stimulation at the epiphyseal plates.

fever; hypoglycemia; stress; vasopressin (ADH)

Internal and external factors that alter the normal ACTH rhythm by triggering CRH release include ________, _______________, and ________ such as trauma, pain, fear, and also by posterior pituitary peptide ______________.

inhibin

LH and FSH control of release: In the male, FSH also stimulates the Sertolic cells of the testes to produce a peptide, _________ which provides the main direct negative feedback control fo the FSH biosynthesis and release from the anterior pituitary. In the female, a similar peptide released by granulosa cells of the developing ovarian follicle, appears to serve a similar inhibitory function on FSH secretion.

somatomedins; IGF-1

Many of the actions of GH on bone and peripheral soft tissue growth are mediated indirectly by the GH-induced production of _________________ (general term for substances released from the liver released in response to GH that have a SIMILAR effect to GH in the body) or _____ in the liver.

hypersecretion of prolactin

May result from pituitary tumor (prolactinoma), interruption of the hypothalamic-hypophysial tract or hypothalamic disease. Increased prolactin because of the loss of tonic inhibition by DA Principle symptoms include infertility and galactorrhea (inappropriate nonpregnant milk production) as well as menstrual complaints. Caused by inhibition of GnRH secretion by the high prolactin levels.

distal tubule; collecting duct

Mechanisms of increase in water permeability (kidney): Increase the water permeability of principal cells in the lateral _______ ___________ and ______________ _______.

hypothalamus; oxytocin

Milk is stored in small milk ducts. Suckling at the breast stimulates the sensory nerves innervating the nipples relay the information to the _________________. ___________ is then released into the circulation from the posterior pituitary, which targets the specialized myoepithelial cells surrounding the milk-producing glands. As these cells contract, milk is forced from the breast into the mouth of suckling infant. (Positive feedback mechanism).

V2 receptor; concentrated

Nephrogenic diabetes insipidus: The posterior pituitary is normal but the principal cells of the collecting duct are unresponsive to ADH due to a defect in the ___ ____________, G2 protein, or adenyl cyclase. Water is not reabsorbed in the collecting ducts and the urine cannot be ________________, resulting in excretion of large volumes of dilute urine. As a result, the body fluids become concentrated and the serum osmolality increases.

paraventricular nuclei

Oxytocin release: Sensory receptors in the nipple transmit impulses to the spinal cord via afferent neurons. This information then ascends in the spinothalamic tract to the brain stem, and finally to the __________________ ___________ of the hypothalamus.

rhythmic contractions; receptors

Oxytocin: At a very low concentration, it causes powerful ___________ _______________ of uterine smooth muscle, promoting labor and delivery. The number of oxytocin _____________ in the uterus peaks near the end of pregnancy, and uterine smooth muscle becomes more and more sensitive to the stimulatory effects of oxytocin.

stimulate; inhibit

Pain, nausea, hypoglycemia, and various drugs (nicotine, opiates, antineoplastic agents) can also ___________ ADH secretion. Alcohol and caffeine can _________ ADH release and cause copious urine output (alcohol-induced diuresis).

GH excess

Patients suffering from ____ _________ can thus show a mild hyperglycemia and insulin resistance.

infundibulum

Pituitary gland: -Located in a bony hollow at the base of the brain -Connects to the hypothalamus superiorly by the funnel shaped __________________ (pea on a stalk)

neurohypophysis; neurohormones; storage area

Pituitary gland: -Posterior lobe + infundibulum make up _____________________ -Composed largely of pituicytes (glia-like supporting cells) and axon terminals originating in either supraoptic or paraventricular nuclei of the hypothalamus ** Releases ____________________ that it receives ready-made from the hypothalamus ** ** A hormone __________ ______, not a true endocrine gland in the precise sense **

hypothalamic-hypophyseal portal

Pituitary gland: Anterior: -Adenohypophysis (Adeno = gland) -Composed of glandular tissue, secretory endocrine cells -Hypothalamus and anterior pituitary are linked via the ________________ _______________ _________ blood vessels -Manufactures and releases a number of hormones

circadian rhythm

Plasma levels of prolactin show a distinct ____________ __________ (highest level at night) in both males and non-pregnant females. This rhythm disappears during pregnancy and lactation, when prolactin release is at its highest.

neuropeptides

Posterior pituitary, made largely of supportive pituicytes and axon, stores ________________ - antidiuretic hormone (ADH) and oxytocin, which have been synthesized and forwarded by hypothalamic neurons of the supraoptic and paraventricular nuclei, respectively.

ADH; oxytocin; supraoptic; paraventricular

Posterior pituitary, made largely of supportive pituicytes and axon, stores neuropeptides - _____ and ____________, which have been synthesized and forwarded by hypothalamic neurons of the ______________ and ___________________ nuclei, respectively.

stored hormones

Posterior pituitary: Cell bodies of ADH neurons: in the supraoptic nuclei of the hypothalamus. Cell bodies of oxytocin neurons: in the paraventricular nuclei of the hypothalamus. These hormones are synthesized and transported along their length to their axon terminals in the posterior pituitary. When these hypothalamic neurons fire, they release the ___________ ____________ into a capillary bed in the posterior pituitary for distribution throughout the body.

neural; hypothalamus

Posterior pituitary: Maintains its _________ connection with the _________________ via a nerve bundle called the hypothalamic-hypophyseal tract, which runs through the infundibulum.

TSH/thyrotropin

Primary action: Stimulates the thyroid gland to secret tri-iodothyronine (T3) and thyroxine (T4). Much more T4 than T3 in blood, but T3 is more potent.

GH

Produced by somatotrophic cells of the anterior pituitary Most abundant of the pituitary trophic hormones The single most important hormone for normal growth to adult stature (not only height, but breadth, muscles and cartilage and such) Can influence a variety of target tissues Single chain peptide containing 191 AA

dopamine

Prolactin exerts a stimulatory short-loop negative feedback effect on the hypothalamic dopamine-secreting neurones, thereby inhibiting its own release, through _____________.

dopamine

Prolactin-inhibiting hormone can act as...

V1; IP3; Ca2+

Receptor for ADH on vascular smooth muscle is a ___ receptor, which is coupled to phospholipase C via a Gq protein. The second messenger is ____ / _____, which produces contraction of vascular smooth muscle, constriction of arterioles, and increased total peripheral resistance.

LH, FSH (gonadotropins)

Regulate the function of the gonads (ovaries and testes)

releasing; inhibiting

Relationship of the hypothalamus to the anterior pituitary -Both neural and endocrine -Because ___________ and ___________ factors are made in the brain

neural; endocrine

Relationship of the hypothalamus to the anterior pituitary: both ________ and ______________

neural

Relationship of the hypothalamus to the posterior pituitary: only __________

prolactin

Single chain peptide (198 AA) with a chemical structure very similar to growth hormone. Responsible for milk production and also participates in the development of the breasts. In nonpregnant, nonlacting females and in males, blood levels of it are low. During pregnancy and lactation, blood levels of it increase, consistent with its role in breast development and lactogenesis (milk production).

ACTH (corticotrophin)

Single-chain peptide hormone consists of 39 amino acids. Derived from a larger precursor, pro-opiomelanocortin (POMC). Stimulates the adrenal cortex (outer portion of the adrenal gland) to release corticosteroid hormones, most importantly glucocorticoids, (mainly cortisol) that help the body to resist stressors, and also small amounts of sex hormones (androgens and estrogens).

Pregnancy (estrogen), Breast-feeding, Sleep, Stress, TRH, Dopamine antagonists

Stimulatory factors for prolactin:

afferent; oxytocin; positive

Stretching of the uterus and cervix as birth nears dispatches ____________ impulses to the hypothalamus, and the hypothalamus responds by synthesizing ____________ and triggering its release from the neurohypophysis. As blood levels of oxytocin rise, the expulsive contractions of labor gain momentum and finally end in birth. (____________ feedback mechanism).

neurogenic diabetes insipidus

Syndrome marked by the output of huge amounts of dilute urine (polyuria) and intense thirst. Body fluid become concentrated (e.g. increased serum osmolality, increased serum Na+ concentration). Can be caused by a blow to the head that damages the hypothalamus or the posterior pituitary releasing site. Failure of the posterior pituitary to secrete ADH.

TRH; pregnancy; cold

TSH released from the thyrotroph of the anterior pituitary is stimulated by the hypothalamic peptide ______. Indirectly by ______________ and _______ temperature.

thyroid; somatostatin

TSH secretion can be inhibited by circulating ___________ hormones at the pituitary level (direct negative feedback) ____________________: released by hypothalamus to reinforce the blockade of TSH release (inhibiting factor)

hCG

The _______, produced by the placenta during pregnancy, has similar structure to LH, and exhibits LH-like activity.

supraoptic nucleus

The increase in NA+ is sensed by osmoreceptors in the anterior hypothalamus, which then transmit excitatory impulses to the hypothalamic neurons in the ____________ ___________ which synthesize and release ADH from posterior pituitary.

nephrogenic diabetes insipidus

The posterior pituitary is normal but the principal cells of the collecting duct are unresponsive to ADH due to a defect in the V2 receptor, G2 protein, or adenyl cyclase. Water is not reabsorbed in the collecting ducts and the urine cannot be concentrated, resulting in excretion of large volumes of dilute urine. As a result, the body fluids become concentrated and the serum osmolality increases.

oxytocin

The posterior pituitary peptide _____________ is also a powerful releasing agent for prolactin, and may be involved in the suckling-induced response. During breast-feeding, serum prolactin levels can increase to more than tenfold the basal levels. Possible mediators are TRH, oxytocin (which is secreted by the posterior pituitary in response to suckling)

V2 receptor; camp

The receptor for ADH on the principal cells is a ____ ___________, which is coupled to adenyl cyclase via a Gs protein. The second messenger _______, via phosphorylation steps, directs the insertion of water channels, aquaporin 2, in the luminal membranes.

inhibitory; stimulatory

This milk-let down reflex can be modified by any factor that affects the hypothalamus such as anxiety, stress and other factors preventing the flow of milk, even the mammary glands are fully functional. (_____________ effects) Nursing mothers can become conditioned to associate a baby's crying with suckling, which then begin milk let-down as soon as they hear a baby cry. (_______________ effects)

somatostatin analogues

Treatment of hypersecretion of GH: _______________ ___________ (e.g. octreotide), inhibit GH secretion by the anterior pituitary.

sexual arousal; orgasm

Until recently, oxytocin's role in males and nonpregnant, nonlactating females was unknown. Recent studies reveal that it plays a role in __________ _________ and __________ when the body is already primed for reproduction by sex hormones; Circulating concentrations of oxytocin in both genders rise during the former and peak at the latter. Then it is responsible for the feeling of sexual satiety or satisfaction that results from that interaction.

IL-1, IL-6, TNF-alpha

Various cytokines, including ___ and ____ and _______ released by macrophages, monocytes, endothelial cells and lymphocytes during inflammatory/immune responses, have a direct stimulatory effect on hypothalamic CRH and pituitary ACTH release.

dopamine, bromocriptine, somatostatin, prolactin

What are four inhibitory factors for prolactin?

breast suckling, dilation of cervix, sight/sound/smell of infant, orgasm

What are some factors that influence the control of oxytocin release?

GRH (gonadotropin releasing hormone); CRH (corticotrophin releasing hormone); TRH (thyrotrophin releasing hormone); GHRH (growth hormone releasing hormone); prolactin-releasing hormone (thyrotrophin releasing hormone, prolactin); prolactin-inhibiting hormone (dopamine)

What are the six hypothalamic releasing and inhibiting hormones that influence the anterior pituitary?

breast development; lactogenesis

What are the two actions of prolactin?

adrenocorticotrophin

What does corticotrophin releasing hormone cause to be released from the anterior pituitary?

LH, FSH

What does the gonadotropin releasing hormone (in the hypothalamus) cause to be released from the anterior pituitary?

TSH (thyroid stimulating hormone)

What does thyrotrophin releasing hormone cause to be released from the anterior pituitary?

somatotrophin

What is the other name for growth hormone?

cAMP

With the possible exception of growth hormone and prolactin, for which the mechanism is incompletely known, all anterior pituitary hormones affect their target cells via a ________ second-messenger system.

LH

_____ is inhibited by feedback inhibition exerted by estrogen and progesterone in females and testosterone in males.

CRH; cortisol; negative

ACTH release is controlled mainly via hypothalamic ______ and regulated by circulating _________ (direct and indirect ___________ feedback)

diurnal; CRH; ACTH

ACTH secretion has a basically _____________ rhythm, with low level around midnight-peak early in the morning. Rising levels of glucocorticoids feed back and block secretion of ______ and consequently _______ release.

nerve impulses

ADH and oxytocin from the posterior pituitary are later released "on demand" in response to ________ ____________ from the same hypothalamic neurons.

phospholipase

ADH and oxytocin, each composed of 9 amino acids, are almost identical but have very different physiological effects on their target organs. Both hormones use the ___________________ second-messenger mechanism to exert their effects on their target cells.

increased blood osmolality, hypovolemia

ADH control of release is primarily influenced by:

neurohypophysis; kidney tubules

ADH is liberated into the blood by the ________________, and targets the _________ ________

reabsorbed

ADH: the increased water permeability of the principal cells allows water to be _______________ by the collecting ducts. This makes the urine concentrated or hyperosmotic, reduce urine volume, and increases the blood volume (reduces osmolality).

increase in water permeability, contraction of vascular smooth muscle

Actions of ADH: