a) Function: synthesis and release of messengers (hormones) into the circulation that act on target tissues
b) Hormones include: steroids, amino acid analogues, peptides and proteins
c) Hormones function to maintain homeostasis

a) rich capillary network (typically fenestrated) to facilitate release of hormone into systemic circulation
b) cellular organelle content related to secretory product released

- extensive mitochondria and smooth endoplasmic reticulum for steroid synthesizing cells
- extensive Golgi, rER, and secretory vesicles for protein, peptide, and amino acid analogue secreting cells

c) intracellular pathways (signal transduction - st) for hormone function is either via transciptional regulation or via membrane receptors/second messenger pathways (and both in some cases):

- transciptional regulation pathway takes hours to days for response
- membrane receptor/second messenger takes seconds to minutes (phosporylation/Ca2+)

III. Pituitary gland (hypophysis)

a) Structure: two regions:

i) neurohypophysis (posterior lobe):

- neural stalk
- pars nervosa

ii) adenohypophysis (anterior lobe):

- pars distalis (major portion of adenohypophysis)
- pars tuberalis (wraps around neural stalk)
- pars intermedia ( residual region of Rathke's pouch)
- anterior lobe = pars distalis and pars tuberalis

b) Embryogenesis:

i) neurohypophysis derived from neuroectoderm

-nerve tissue (axon terminals) and support cells

ii) adenohypophysis derived from oral ectoderm

-secretory epithelial cells

c) Cells, secretory products, and sites of action:

i) pars nervosa: made of axons from secretory neurons in the hypothalamus and of glial-like cells called pituicytes; hormones (peptides and small proteins) are stored in granules at the axon terminal which accumulate to form Herring bodies; the hormones released, site of action, and effects are:

- a nonapeptide called vasopressin (antidiuretic hormone, ADH):st via membrane receptor /kinases on the cells of:

- kidney:increases water permeability in collecting ducts giving hypertonic urine-vascular smooth muscle: requires high levels and results in contraction

- a nonapeptide called oxytocin: st via membrane receptors>kinases on the cells of:

- uterus: stimulates uterine smooth muscle contraction during copulation and parturition
- mammary gland: stimulates myoepithelial cell contraction aiding in milk release

ii) adenohypophysis (pars tuberalis, pars distalis, pars intermedia):

- pars distalis: made of secretory epithelial cells that secrete:

- a protein called somatotropin (growth hormone): st via a membrane receptor/ kinase pathway leading to increased expression and secretion of IGF (I and II) and IGF binding proteins in the cells of:

- liver, kidney (circulating), other organs/tissues (paracrine): stimulates growth of muscle, cartilage, and bone, decreases fat,, increases lactation (used commercially to increase milk production in dairy cows)

- a protein called prolactin: st via a membrane receptor/kinase pathway leading to transcriptional regulation in the cells of:

- mammary gland: stimulates development (ducts and secretory cells) during pregnancy and lactogenesis after parturition

- a dimeric glycoprotein protein called follicle-stimulating hormone (FSH): st via membrane receptor/kinase leading to transcriptional regulation that in the cells of:

- gonads: stimulates ovarian follicle development and spermatogenesis in the testes

- a dimeric glycoprotein called luteinizing hormone (LH): st via membrane receptor/kinase pathway leading to transcriptional regulation in the cells of:

- gonads: maturation of the ovarian follicle, ovulation, corpus luteum formation, stimulation of steroid secretions from ovarian follicle and corpus luteum; maintenance of testicular Leydig cells and their secretion of androgens

- a dimeric glycoprotein called thyrotropin (TSH):st via a membrane receptor/kinase pathway leading to transcriptional regulation in the cells of:

- thyroid gland: stimulates growth of thyroid epithelial cells and their release of thyroid hormone

- a small peptide called corticotropin (adrenocorticotropic hormone, ACTH): st via membrane receptor/kinase pathway leading to transcriptional regulation in the cells of:

- adrenal gland: stimulates synthesis/secretion of glucocorticoids and gonadocorticoids from adrenal cortex

- pars tuberalis -FSH and LH
- pars intermedia -? melanocyte-stimulating hormone, endorphin

d) Control of secretion:

i) pars nervosa:

- neurohypophysis is a nerve track in which cell bodies from the hypothalamus send axons through the neural stalk (median eminence and infundibulum).

- axons of supraoptic and paraventricular nuclei terminate in pars nervosa
- secretion of oxytocin and vasopressin via neural excitation of their respective cell bodies in the hypothalamus

- dorsal and ventral medial and infundibulary nuclei terminate in the neural stalk and their secretions control many tropes in the pars distalis

ii) pars distalis

- hypothalamic derived neurosecretory cells in the median eminence that secrete:

-Thyrotropin-releasing hormone (TRH): stimulates TSH release
-Gonadotropin-releasing hormone (GnRH): stimulates FSH and LH release
-Growth-hormone-releasing hormone (GRH): stimulates growth hormone release
-Corticotropin-releasing hormone (CRH): stimulates release of ACTH
-Somatostatin: inhibits release of growth hormone and TSH
-Prolactin-inhibiting hormone (dopamine): inhibits release of prolactin

e) Blood supply:

i) blood supply from internal carotid artery via superior and inferior hypophyseal arteries

- superior hypophyseal arteries supply median eminence and infundibulular stalk
- inferior hypophyseal arteries supply pars nervosa

ii) the pars distalis has no direct arterial supply, blood first passes through the primary capillary plexus in the neural stalk and pars tuberalis which drain into the hypophyseal portal veins which then empty into the secondary capillary plexus in the pars distalis. This hypophyseal portal system carries hormones from the neural stalk to the pars distalis.

IV. Pineal gland

a) Structures: very small gland located just above and connected to the diencephalon portion of the brain, parenchyma made primarily of pinealocytes and astrocytes (glial cells), gland develops calcified structures called corpora arenacea or brain sand which is used as a radiologic land mark

b) Secretory products and sites of action: melatonin (a amino acid analogue) is synthesized and secreted by Pinealocytes, melatonin has some influence on gonads (inhibits steroidogenic activity) and possibly other organs in relation to daylight length (seasonal affective disorder- SAD).

c) Control of secretion: melatonin secretion increases during darkness and decrease during daylight via sympathetic nerve relays from the photoreceptors of the retina

d) Blood and nerve supply: blood supply typical of endocrine glands with no specialized portal system, nerve supply via sympathetic nerves relaying information from the visual system (light intensity and duration)

V. Thyroid glands:

a) Structures: bilobed gland in the neck (near larynx) arranged in follicles made mostly of simple epithelial cells surrounding a protein-filled (thyroglobulin) lumen. Functional cells of the thyroid are follicular and parafollicular cells

b) Cells, secretory products, and sites of action:

i) follicular epithelia cells: actively uptake iodide and amino acids, synthesize thyroglobulin and glycosylate it, oxidize iodide, transport both thyroglobulin and oxidized iodide to follicle lumen, iodination occurs within the follicle, iodinated thyroglobuline taken into the cell by pinocytosis, iodinated tyrosine residues removed, and secrete:

- iodinated amino acid analogues called triiodothyronine (T3) and tetraiodothyronine (T4): st via proteins that bind the hormone and then bind DNA regulating transcriptional activity of the cells of:

- many organs and tissues; increase basal metabolic rate, growth, and development

ii) parafollicular cells synthesize and secrete:

- a proteins called calcitonin: st via membrane receptor/kinases in the cells of:

- bone: decreases ostoeclastic activity (weakens attachment to bone)
- kidney: increases excretion of calcium in "neonatal" urine (does not reclaim it)

c) Control of secretion:

i. triidothyronine and tetreiodothyronine synthesis is stimulated by thyroid stimulating hormone (TSH) from the adenohypophysis

ii. calcitonin release stimulated by elevated blood calcium via serum calcium sensors "tasting" intercellular fluid calcium

d) Blood supply: extensive network of capillaries and lymphatic capillaries for transport.

VI. Parathyroid glands:

a) Structures: encapsulated small glands adjacent to the thyroid gland, parenchyma is made mostly of principal (chief) cells and partly of oxyphil cells

b) Cells, secretory products and sites of action:

i) principal (chief) cells synthesize and secrete:

- a protein hormone called parathyroid hormone: st via membrane receptor/kinase in the cells of:

- bone: increasing bone resorption by osteoclasts stimulation from cytokines of osteoblasts
- kidney: decrease calcium and increase phosphate in "neonatal" urine (increase calcium resorption and decrease phosphate resorption in proximal, conv. tubule)
- small intestine: increase intestinal adsorption of calcium indirectly by enhancing formation of 1,25-dihydroxycholecalciferol (active Vit. D) in the kidney; activeVit. D stimulates calcium absorbtion by intestinal epithelia

c) Control of secretion: control of parathyroid hormone secretion is directly by serum calcium

d) Blood supply: blood supply via inferior thyroid arteries, nerve supply of vasomotor function only

VII. Islets of Langerhans: clusters of endocrine cells within the exocrine pancreas

a) Structures: polygonal cells arranged in clusters or cords called islets. The islets constitute 1-2% of pancreatic volume. Cell can be distinguished by special staining techniques giving A, D and B cells, each having different secretory products.

b) Cells, secretory products and sites of action:

i. B-cells:

- secrete a dipeptide called insuln: st via membrane receptor/kinase in the cells of:

- liver, muscle, and fat: stimulate glucose uptake, glyconeogenesis (liver and muscle) and lipogenesis (fat)

ii.A-cells:

- secrete a peptide called glucagon: st via membrane receptor/kinase in the cells of:

- liver: stimulates gluconeogenesis (via amino acids) and glycogenolysis
- fat: stimulates fat catabolism

iii. D-cells:

- secrete a cyclic polypeptide called somatostatin:st?, influence

- pars distalis>somatotropes, inhibits somatotropin synthesis and secretion

c) Control of secretion:

i) parasympathetic stimulation increases secretion of insulin and glucagon
ii) sympathetic stimulation increase secretion of glucagon and inhibits secretion of insulin
iii) several blood borne molecules (hormones, glucose, amino acids, fatty acids) influence secretion of insulin and glucagon

d) Blood and nerve supply:

i) arterioles branch into capillaries at the islet periphery first perfusing the A and D cells then the B cells. Blood flow: A and D cells > B cells > exocrine pancreas.

ii) parasympathetic and sympathetic neurons innervate the islets with about 10% of the cells receiving direct neural contact and the remainder communicate via gap junctions

VIII. Adrenal glands

a) Structures: half moon-shaped structures near the superior poles of kidneys, gland covered by a collagenous capsule and organized into two concentric layers called:

i) adrenal cortex:

- zona glumerulosa (15%)
- zona fasciculata (65%)
- zona reticularis (7%)

ii) adrenal medulla

b) Embryogenesis:

i) adrenal cortex derived from coelomic intermediate mesoderm
ii) adrenal medulla derived from the neural crest ectoderm

c) Cells, secretory products, and sites of action:

i) adrenal cortex: steroids

- parenchymal cells of the zona glumerulosa: columnar or pyramidal cells arranged in clusters surrounded by capillaries that release:

- a steroid called mineralocorticoids (aldosterone): st via proteins that bind the hormone and then bind DNA regulating transcriptional activity in cells of:

-kidney, stomach, and salivary glands: stimulates resorption of Na+ and stimulates excretion of K in kidney ("post-pubescent urine")

- parenchymal cells of the zona fasciculata: polyhedral vacuolated cells arranged in cords along capillaries that secrete:

- a steroid called glucocorticoid (cortisol and corticosterone): st like aldosterone influencing the cells of:

- many organs:carbohydrate, protein and lipid metabolism and depress immune response; stimulate gluconeogenesis and glycogenesis in liver; stimulate protein and lipid catabolism in muscle and adipose tissue

- steroids called androgens (dehydroepiandrosterone): sex hormone which has weak masculinizing and anabolic activity

- parenchymal cells of the zona reticularis: smaller irregular-shaped cells arranged in anastomosing cords surrounded by capillaries that secrete:

- glucocorticoid and androgens as fasciculata

ii) adrenal medulla: cords of polyhedral cells surrounded by capillaries; similar to sympathetic postganglionic neurons, without processes, that secrete:

- amino acid analogues (catecholamines) called epinephrine and norepinephrine: st via membrane receptor/kinase in cells of many organs of the body

- fight or flight response in tissues, increase rate of respiration and dilate bronchioles, increase heart rate and blood pressure, stimulate glycogenolysis in muscle and liver, stimulate secretions of sweat glands, decrease blood flow through and activity of digestive tube

d) Control of synthesis or secretion:

i) adrenal cortex: regulate via synthesis

- angiotensin and ACTH stimulate mineralocorticoid synthesis in the zona glumerulosa
- corticotropin stimulates androgen and glucocorticoid synthesis in zona fasciculata and reticularis

ii) adrenal medulla: regulate secretion

- catecholamine release stimulated by preganglionic sympathetic neurons form a terminal on the cell body (axio-somatic junction)

- glucocorticoid via cortical sinusoids stimulate conversion of norepinephrine to epinephrine, thus epinephrine-secreting cells in areas supplied by cortical sinusoids and norepinephrine cells in areas supplied by medullary arteriole

e) Blood supply:

i) arterial supply enters from several sources forming a sub-capsular plexus, from the plexus, three groups of arteries emerge:

- capsular arterie
- cortical arteries that form capillary beds in the cortex which drain into the medulla
- medullary arterioles that pass through the cortex and form capillary beds in the medulla

ii) the medulla receives arterial blood from the medullar arterioles and venous blood via the cortical capillaries. Medullary and cortical blood drain into small medullary veins which drain into the large medullary (adrenal or supra-renal) vein