Endocrine

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trophic hormones

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- modulate secretory activity of other endocrine glands, acts on other endocrine cells

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direct-acting hormones

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stimulate changes in non-endocrine tissue, act directly on the cells or tissues where the change will be established

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hormone producing cells

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- they synthesize hormones and secrete them into extracellular fluid
- hormones then immediately enter blood vessels or lymphatic vessels and are transported to other tissues
- even though hormones first pass through the extracellular space, we simply state that they are secreted into the blood or the lymph
- a given hormone affects only certain cells of certain organs which are referred to as target cells or target organs
- hormone producing cells and their targets may be located in the same organ or tissue

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hormone action

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- the main action of a hormone is to stimulate change in the target cell's metabolism
- hormone-induced alterations in target cells include alterations of the cell membrane permeability, stim of protein synthesis, activation or inactivation of enzymes or stim of target cell replication
- in order for a target cell to respond to a specific hormone, the target cell must have receptors or binding sites which attach specifically to the hormone
- these receptors may be located on the target cell plasma membrane or in the cell nucleus
- binding of a hormone to a target cell receptor triggers a series of intercellular reactions which ultimately results in changes in target cell metabolism

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endocrine system

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- it includes hormone-producing cells which are located throughout the body in many different organs
- the organs classified as endocrine glands function primarily in hormone production with the testes and ovaries considered both reproductive organs as well as endocrine glands

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control of hormone secretion

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1. humoral - composition of EC fluid
2. hormonal
3. neural
and negative feedback inhibition

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histological features

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- CT capsule, septa, and stroma
- many glands have a reticular fiber framwork that surrounds glandular cells and capillaries
- highly vascular - fenestrated capillaries

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hypothalamus

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neuroendocrine regulation
- autonomic control over adrenal medulla
- neuronal synthesis of hormones, axons extend into pars nervosa
-- supraoptic nucleus: neurons synthesize ADH
--paraventricular nucleus: neurons synthesize oxytocin
- secretion of regulatory hormones that control anterior pituitary secretion
-- releasing factors
-- inhibiting factors

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pituitary gland (hypophysis)

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derived from ectoderm, lots of unmyelinated axons, at the end is terminal boutons

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posterior pituitary (neurohypophysis)

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- develops as a downgrowth of hypothalamus, derived from neuronectoderm
- median eminence: extension of the hypothalamus into posterior pituitary
- pituitary stalk = infundibulum
- Pars nervosa

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Pars Nervosa

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- unmyelinated axons of neurons whose NCBs are located in the hypothalamus
- Herring bodies: secretory granules in dilated axon terminals
- Pituicytes: dont secrete hormones, they are support cells
- Hormones: synthesized by neurons in the hypothalamus, travel down axons into posterior pituitary and are secreted by the posterior pituitary
-- ADH: increases DCT and collecting tubule permeability, water is absorbed creating hypertonic urine
-- diabetes insipidus: chronic renal disease caused by genetic defects in receptors for ADH and or nonresponsive receptors for ADH
- Oxytocin: myoepithelial cell contraciton in mammary gland, contraction of uterine smooth muscle during labor, smooth muscle contraction in the uterus

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anterior pituitary (adenohypophysis)

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- develops from outpocket of oral ectoderm = Ratke's pouch
- pars tuberalis
- pars intermedia
- pars distalis

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pars tuberalis

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- partially enwraps adjacent infundibulum

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pars intermedia

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- clefts or cyst-like spaces [where they fuse together] = remnants of ratkes pouch
- secretory cells: melanocyte stimulating hormone (MSH) and a small amount of ACTH

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pars distalis

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secretory cells arranged in cords around capillaries

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Pars distalis H & E sections

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1. Chromophobes: support cells and stem cells
2. Chromophils
- Acidophils
-- Somatotrophs
-- Mammotrophs
- Basophils
--corticotrophs
--thyrotrophs

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somatotrophs: Growth Hormone (GH)

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- stim liver production of insulin-like growth factor 1 which stim cell growth and protein synthesis in most body tissues, esp. bone
- controlled by hypothalamic growth hormone - releasing factor and somatostatin
- decreased GH: dwarfism
- increased GH in children: giantism
- increased GH in adults: acromegaly, HTN, changes in bone structure

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mammotrophs (lactotrophs): prolactin

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- stim milk production and growth and development of mammary glands during pregnancy
- inhibitory factors: DA, estrogen, and progesterone
- hypothalmic prolactin-releasing factor and thyrotropin-releasing factor stim prolactin release
- prolactin-secreting tumors: anovulation in females, decreased libido, infertility and galactorrhea in males

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corticotrophs: ACTH, corticotropin

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- stim secretion by adrenal cortex cells, acts on two zones to syn hormones and secretions of glucocorticoid and steroids
- controlled by hypothalamic corticotropin releasing factor

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thyrotrophs: Thyroid-stimulating hormone (TSH)

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- stim by hypothalamic thyrotropin releasing factor
- inhibited by T3 and T4

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gonadotrophs: follicle stimulating hormone (FSH) and leutinizing hormone (LH)

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- a single cell can syn both FSH and LH
- controlled by hypothalamic gonadotropin releasing factor
- pituitary tumors, anorexia, can decrease secretion of GrRF causing decreased fertility in females and hypogonadism in males

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blood supply: inferior hypophyseal artery

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pars nervosa

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blood supply: superior hypophyseal artery

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- hypothalmus, infundibulum, pars tuberalis, [fenestrated capillary network]
- portal veins
- fenestrated capillary network of the anterior pituitary

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thyroid gland

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- secretory cells: follicle cells and parafollice cells, butterfly shaped gland, 4 PTH glands embedded in it, only glands that stores its secretory product outside of the cells

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follicle cells

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- thyroid follicle: cuboidal to squamous cell on basal lamina surround central colloid filled lumen
- appearance of follicles reflect activity of cells
- colloid = thyroglobulin; glycoprotein complexed with T3 and T4
- follicle cells synthesize: T3 and T4
- T3 and T4 stim cell metabolism

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follicle cell synthesis of T3 and T4

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- basal iodide pump: iodide oxidized to iodine at apical plasma membrane
- thyroglobulin synthesis, thyroglobulin iodinated in colloid at apical cell surface
- TSH stim endocytosis of thyroglobulin
- thyroglobulin fuses with lysosomes, T3 + T4 cleaved and secreted

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parafollicular cells (C - cells)

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- secrete calcitonin
- high blood calcium - parafollicular cells secrete calcitonin - this will inhibit osteoclast bone absorption, stimulates osteoblasts - causes a decrease in blood calcium

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cretinism

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- congenital absence of the thyroid, profound neurological damage, defeciency that is a type of hypothyroidism, profound effects on development in children

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graves disease

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- autoimmune, antibodies to TSH receptors actually mimic TSH and chronically activate the follicle cells, so you have excessive T3 and T4 secretion
- enlarged thyroid (goiter), exopthalmus. tachycardia, fine finger tremors

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hypothyroidism

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- congenital hypoplasia of pituitary: decreased cell metabolism, mental lethargy, hypothermia, myxedema
- Hashimoto's disease: autoimmune, antibodies to thyroglobulin, destruction of follicles,
- insufficient dietary iodine,
- other thyroid diseases

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parathyroid glands

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- cheif (principle) cells: secrete parathyroid hormone (PTH)
- low blood calcium levels stim the secretion of PTH
- PTH binds to osteoblasts and influences osteoblast regulation of osteoclast differentiation and function. The net result is an increase in osteoclast resorption of bone
- Low blood calcium leads to PTH secretion which causes:
1. stim osteoclast resorption of bone
2. increases renal tubular reabsorption of calcium
3. increases small intestine absorption of calcium
the net result is increased blood calcium
- Oxyphils: may be a form of cheif cells, may be a stem cell
- Aging: CT and adipose infiltrate the PT gland

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Hyperparathyroidism/ Hypoparathyroidism

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- can be a genetic mutation of cheif cells, cells can't sense blood calcium levels
- benign adenomas of gland can cause hyperparathyroidism, Increased PTH causes increased bone demineralization and calcium excretion [leads to renal calculi]
- idiopathic hypoparathyroidism: tissues dont respond to PTH

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adrenal gland

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- CT capsule, septa, reticular fibers
- cortex derived from mesoderm
- medulla derived from neural crest

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cortex

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- zona glomerulosa
- zona fasciculata
- zona reticularis

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zona glomerulosa

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- thin zone, right underneath the CT capsule
- packed clusters or columns of cells
- secretes mineralcorticoids, mainly aldosterone: maintain salt conc. of the blood by increasing absorption of Na in the DCT of the kidney, sweat glands, and intestines
- secretion of aldosterone is stim by low salt conc in the blood and low BP, through ACTH may also stim secretion

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zona fasciculata

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- widest layer
- long straight columns of foamy cells
- ACTH stim secretion
- secretes glucocorticoids: cortisol (converted into cortisone by hepatocytes)
- promotes glucose metabolism in the liver and promotes lipid and protein degradation, promotes gluconeogenesis
- anit-inflammatory, suppresses immune system

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zona reticularis

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- anastomosing cords of cells
- ACTH stim secretion
- secretes androgens: DHEA, androstenedione
- androgens converted to testosterone and estrogen in peripheral tissue
- main source of estrogen in post-menopausal women

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adrenal cortex functions

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- in early gestation, fetal adrenal cortex secretes dehydroepiandrosterone which is a precursor to placental hormones
- during 1st year, fetal adrenal cortex degradates and is replaced by adult cells

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Cushing's Disease

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- caused by an ACTH-producing tumor in the pituitary, which stim the adrenal cortex
- overproduction of cortisol leads to fat redistribution and muscle wasting as well as immunosuppression
- increased androgens

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Cushing's Syndrome

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- caused by functional tumor of the adrenal cortex
- can be caused by excessive steroid use

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addison's disease

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- chronic destruction of the cortex caused by autoimmune responses of TB, usually in the fasciculata
- increased ACTH levels due to cortisol deficiency
- hypotension, muscle weakness, increased skin pigmentation

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adrenal medulla

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- chromaffin cells: modified sympathetic postganglionic neurons
- 2 populations of cells: synthesize and secrete epinepherine and NE which are stored in secretory vesicles

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Islets of Langerhans

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round compact mass of cells with capillary network surrounding and entwining. Reticular fiber meshwork separates the Islets from the acinar cells. Clusters of cells separted from the rest of the exocrine pancreas

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Pancreas: main cell types

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1. Alpha cells: glucagon induces hepatic glycogenolysis
2. Beta cells: secrete insulin, will absorb glucose via the GLUT 2 transport proteins and the glucose will enter the beta cell and stim the release of insulin, then it will bind to peripheral cells and stim the uptake of insuln by the body
- delta cells: somatostain, gastrin
- F cells: pancreatic polypeptide inhibits SS
- other cell types are present, and other hormones are secreted by A, B, and D cells

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insulin synthesis

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- glucose enters B cell via GLUT 2 and stim cell syn and secretion of insulin, GLUT 2 is an insulin dependent transporter
- binds to insulin receptors on body cells
- insulin triggers a reaction that facilitates glucose uptake in body cells by GLUT 4 transports, GLUT 4 transporters are insulin dependent
- GER to preproinsulin to cleave to proinsulin to cleaved and packaged in the golgi to insulin transported by microtubules to cell surface and secreted

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blood glucose regulation

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- above normal range: leads to insulin secretion that leads to stimulate cell uptake of glucose and liver storage of glucose
- below normal range: leads to glucagon secretion leads to increase of liver release of glucose and gluconeogenesis

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diabetes mellitus

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1. Insulin Dependent (Juvenille, Type 1)
- autoimmune destruction of B cells, absent or deficient insulin secretion, ~90% are kids but can occur in adults
2. Adult-onset (non-insulin dependent, Type II)
- genetic predisposition
- insulin levels cna be normal or elevated
- insulin resistance of peripheral target tissues may be due also to increased number of insulin receptors or deficient signaling of GLUT 4 transporter
In both types of diabetes the common symptoms are:
1. high blood glucose levels: levels are abnormally high because cells are not efficiently removing glucose from the blood
2. excessive hunger: cells can not utilize available glucose so they are starved for energy and break down fats and proteins instead
3. high glucose conc. in urine: excess glucose is filtered out in the urine
4. frequent urination and excessive thirst: excess glucose in the urine concentrates it so the kidneys flush out extra water in order to dilute the urine

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pineal gland

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- part of the epithalmus
- consists of neurons, glia, and pinealocytes
- corpora arenacea (brain sand): increases with age, ppt of calcium phosphates and carbonates on carrier proteins
- pinealocytes secrete melatonin
--max syn and secretion is during dark cycles, light suppresses melatonin secretion
-- derived from serotonin
-- regulates sleep/wake cycles
--melatonin inhibits hypothalamic release of og GrRH which inhibits the secretion of FSH and LH
-- may regulate puberty onset