TOB Endocrine I (17)

• ductless glands that synthesize, store & secrete hormones into a small extracellular space where they immediately pass through fenestrated capillaries & enter the blood stream
• their effects are usually systemic

• any cell-cell communication by some diffusible substance could be considered hormonal signaling
• paracrine: one cell releases a product that acts on a neighboring cell
• autocrine: a cell releases a product which can act on ITSELF

any hormone that will act directly on another endocrine organ

• act by binding to cell surface receptors & activating 2nd messenger systems
• protein (larger): prolactin, growth hormone, etc.
• peptide: ADH, oxytocin (9 AA each)

hormones derived from amino acids: phenylalanine, tyrosine, tryptophan thyroxine, melatonin, catecholamines [adrenaline/noradrenaline]

• controlled by the hypothalamus which itself secretes hormones along the hypothalamic-hypophyseal axis
• develops from two different sources:
• up-growth of oral pharynx (oral ectoderm) - anterior pituitary
• down-growth of third ventricle (brain) - posterior pituitary

• includes the:
• 1. pars distalis
• 2. pars intermedia
• 3. pars tuberalis
• is the glandular part of the pituitary

• anterior pituitary
• derived from oral ectoderm: this part of the pituitary is epithelial & secretory in nature
• it has 5 distinct cells: somatotrophs, mammotrophs, thyrotrophs, gonadotrophs & corticotrophs
• AP LABELED

• Rathke's pouch
• remnants of it can be seen in the pituitary, as it's present in the oral pharynx, which is where part of the pituitary develops from
• splits the orally derived portion into the pars intermedia & the pars distalis

• entire pituitary
• anterior = on the right; H&E blue --> cellular, lots of nuclei (almost no CT)
• posterior = on the left; H&E red --> mostly axon tracts extending down from the brain; fewer cells
• O = optic nerve
• sits in the the sella turcica

• hormone secreting cells of the anterior pituitary
• large nucleus actively transcribing DNA --> mRNA
• jam packed w/ granules

• anterior pituitary
• A: acidophils; reddish gradules (somatotrophs & mammotrophs)
• B: basophils; blueish granules (thyrotrophs, gonadotrophs & corticotrophs)
• C: chromophobes; unstained, few granules
• highly cellular organ with clumps = chords of cells separated by fenestrated capillaries

• acidophils that secrete growth hormone (GH) and account for 50% of pars distalis cells
• release of GH is stimulated by GHRH (growth hormone releasing hormone) & inhibited by somatostatin from the hypothalamus
• GH stimulates growth, cell proliferation & regeneration

• acidophil cells that secrete prolactin and account for 15-20% of the cells
• their numbers & size increase during pregnancy
• are controlled by thyroid releasing hormone (TRH) and by vasoactive intestinal peptide
• prolactin stimulates milk production in the mammary gland

• basophils that secrete thyroid stimulating hormone (TSH); account for 5% of pars distalis cells
• are controlled by hypothalamic thyroid releasing hormone (TRH)
• TSH stimulates thyroid gland to secrete thyroxine (T4) & triiodothyronine (T3)

• basophils that secrete follicle stimulating hormone (FSH) + luteinizing hormone (LH)
• account for less than 10% of the total pars distalis cell number
• GnRH and LHRH (luteinizing hormone releasing hormone) controls then from the hypothalamus
• FSH stimulates germ cell maturation while LH triggers ovulation in females and makes Leydig cells males produce testosterone

• basophils that secrete adrenocorticotropic hormone (ACTH), which stimulates the cells of the adrenal cortex to release corticosteroids
• are controlled by corticotropin releasing hormone (CRH)

• Chromophobes
• unclear what they are
• might be degranulated acidophils/basophils
• might be folliculostellate cells
• might be stem cells

• also found in the pars distalis (AP) and form a network between themselves & endocrine cells with numerous gap junctions
• their function is unclear but they might be involved in coordinating endocrine cell function OR serving as stem cells
• they don't contain granules and have a dendritic morphology

• portion of the pituitary derived from oral cavity which contains rathke's pouch remnants, or cysts filled with colloid (specifically found in the space between the pars distalis & pars intermedia)
• the intermedia itself contains cells called corticotropes

• corticotropes are the basophilic (blue) cells found in the pars intermedia (~AP) which make proopiomelanocortin (POMC)
• POMC can be cleaved to form
• 1. MSH (melanocyte stimulating hormone)
• 2. β-endorphin
• 3. ACTH
• 4. β-lipotropin (LPH)

• neurosecretory storage organ; includes the:
• 1. pars nervosa
• 2. infundibulum (stalk)
• is the nervous tissue part of the pituitary; fewer cells, lots of axons (can stain for neurofilaments --> will light up pars nervosa)

• major portion of the posterior pituitary - derived from neural tissue and is an extension of the brain
• contains neuorglial cells, pituicytes, & axons extending from the paraventricular (oxytocin) and supraoptic (ADH) hypothalamic nuclei
• these hormones are stored in Herring bodies, swellings near the axon terminus
• they're released from the hypothalamus & travel along axons in the hypothalamohypophyseal tract into the posterior pituitary
• *the pars nervosa RELEASES hormones only, it doesn't synthesize them

• hormone synthesized in the paraventricular region of the hypothalamus & released from the posterior pituitary
• it controls lactation and uterine contraction

• antidiuretic hormone is synthesized in the supraoptic region of the hypothalamus & released from the posterior pituitary
• it increases water absorption in the collecting ducts of the kidney
• & constricts blood vessels

• carrier proteins that transport oxytocin and vasopressin to the posterior pituitary from the paraventricular and supraoptic nucleus of the hypothalamus
• are secreted from the hypothalamus along with their passenger hormones

• histology of the posterior pituitary (pars nervosa)
• stringyness: unmyelinated axons
• areas w/ blood cells: fenestrated capillaries; LOTS of blood vessels
• large purple dots: pituicytes (type of neural support cells)

• when cysts in the pars intermedia enlarge & their internal colloid leaks, inflammation results
• this sometimes inhibits the release of ADH and causes central diabetes insipidus (central b/c a defect in the CNS)
• if the problem is in the kidneys' responsiveness to ADH, the condition is called nephrogenic diabetes insipidus
• [insipid means tasteless]

• Herring bodies
• good diagnostic marker for posterior pituitary if seen in field

• neuroendocrine gland that's indirectly inhibited by light and active in the absence of light
• main hormone it makes when dark is melatonin
• is an outgrowth of 3rd ventricle shaped like a pine cone

• norepinephrine inhibits the secretion of melatonin
• when light enters the eye it moves through some complicated CNS areas but eventually stimulates sympathetic nerves in the spinal chord which in turn signal back to the pineal gland
• the sympathetic nervous system uses norepinephrine as a NT, therefore if light stimulates it and norepinephrine is being used, melatonin secretion from the pineal gland (in the presence of light) is INHIBITED

pineal gland cell which converts tryptophan --> serotonin --> melatonin ONLY in the darkness

• plays a role in circadian rhythms (sleep cycles)
• disregulation of it can cause jet lag & S.A.D.
• perhaps plays a role in puberty
• and is a powerful antioxidant

• histology of the pineal gland
• subdivided into lobules; some CT separating cells
• w/in lobules are:
• pinealocytes - less dark, can see nucleus
• interstitial cells - darker, thinner cells

• corpora arenacea ("brain sand")
• defining element of the pineal gland, are calcifications, probably accumulated waste products that can't be cleared easily

• 1. Corpora arenacea (brain sand): large, mulberry-like concretions made of hydroxyapatite, protein, glycoprotein that increase with age
• 2. Myeloconia (brain dust): small crystals made of calcite (CaCO3) & glycoprotein; are similar to otoliths of inner ear

compact clusters of epithelial cells richly vascularized with fenestrated capillaries (into which the cells secrete their hormones)

• magenta cells = acini: zymogens secreted through ducts via exocrine mechanism
• light pink clumps = islets: hormones secreted through capillaries via endocrine mechanism

• 1. beta cells: most, secrete insulin (cellular uptake of glucose from blood)
• 2. alpha cells: secrete glucagon (cellular release of glucose into the blood)
• 3. delta cells: produce somatostatin (modulates secretion of insulin & glucagon)

• a paired lobes that sit on top of the trachea derived from a down-growth of oral epithelium from the tongue's base
• an isthmus connects the two lobes (sometimes in section)
• individual lobules are filled with homogenous (pinkish/purplish) colloid, which contains an inactive form of thyroid hormones
• a single layer of follicular cells interspersed with fenestrated capillaries surrounds the lobules

• thyroid
• inactive thyroglobulin is stored extracellularly in a lobule
• also present in this lobule is thyroid peroxidase, which oxidizes iodide (I-) --> iodine (I)

• an iodinated glycoprotein (660kDa) that is the precursor form of thyroid hormone stored in the lumen of each follicle
• contains a lot (120) tyrosine residues which are modified to create the two main thyroid hormones

• the cells that line the follicles
• they synthesize thyroglobulin & take up iodine from capillaries (the blood)
• iodine is released into the colloid & iodinates tyrosine residues in thyroglobulin, creating mono- or di-iodotyrosine
• coupling reactions join iodotyrosine residues forming either tri- or tetra-iodotyrosine linkages
• when TSH (from the anterior pituitary) stimulated the thyroid, iodinated thyroglobulin is cleaved, releasing triiodothyronine (T3) & tetraiodothyronine (T4, thyroxine)
• T3 is the more potent form & regulates metabolic rate, heat production, growth, & development

• eg. Graves' disease: have autoantibodies against TSH receptor
• or cancer of Follicular cells or pituitary (adenoma)
• in both cases there's an overproduction of T4 & T3 that leads to weight loss, muscle weakness, sweating, exophthalmos (bulging eyes), increased apatite
• (thyrotropes)

• due to iodine deficiency
• can be autoimmune or for various reasons have low pituitary TSH release
• results in poor muscle tone, fatigue, cold intolerance, & weight gain

• a lack of iodine makes synthesis of thyroid hormones difficult
• because the body doesn't detect any T3 or T4 being made, there's an increase of TRH from the hypothalamus signaling the pituitary to make more TSH to act on the thyroid
• this stimulation causes hypertrophy (size) & hyperplasia (#) of cells + an increase in colloid --> SWELLING
• follicular cell also develop papillations
• treatment: iodized salt everywhere prevents this from happening

• parafollicular cells (C cells, clear cells)
• cells located deep/basal to the follicular epithelium in the thyroid that synthesize & store calcitonin in granules
• develop from the neural crest
• are controlled only by serum Ca2+ levels

• hormone secreted into the blood stream by parafollicular cells (C cells, clear cells) by high levels of serum Ca2+
• it LOWERS blood calcium levels
• it DECREASES both osteoclast (bone breakdown) activity & Ca2+ absorption
• *not a vital hormone

typically have 2 inferior and 2 superior glands

• hormone made by chief cells that INCREASES blood calcium (the opposite of calcitonin)
• increases osteoclast activity
• stimulates vitamin D activation in kidney, which stimulates Ca 2+ resorption in GI tract & kidney)
• * a vital hormone