Flashcards in Endocrine Glands Deck (77):
What are the three types of endocrine action?
1. True endocrine - release into vasculature
2. Paracrine - affecting nearby cells
3. Autocrine - cell acting upon self
What are the three classes of hormones and what defines the cells that produce them?
1. Peptides / proteins / glycoproteins - prominent ER and golgi with storage vesicles
2. Steroids - prominent smooth ER and mitochondria with lipid droplets. Require specialized plasma carriers
3. Amino acid analogs - i.e. catecholamines like epinephrine and norepinephrine
How does the general mechanism of steroid vs peptide hormones differ?
Peptides generally bind to cell surface and influence the cell via second messenger system
Steroids enter the target cell and bind DNA, causing a change in transcription of proteins / hormone specific response
What is the organization of most endocrine glands with respect to secretory cells + product delivery?
They have no duct system, so they usually appear as clumps or cords of cells surrounded by a dense plexus of fenestrated capillaries.
Where is the hypophysis?
The pituitary gland sits at the base of the brain, and is attached to the hypothalamus via the infundibular stalk. It lies within the sella turcica of the sphenoid bone, and is partly covered by the diaphragma sellae, part of the dura mater.
What are the three parts of the adenohypophysis?
1. Pars tuberalis - part wrapping around the infundibulum
2. Pars distalis - largest portion
3. Pars intermedia - between the pars distalis and pars nervosa
What are the two parts of the neurohypophysis?
It is a downgrowth of the diencephalon that surrounds Rathke's pouch during development.
1. Pars nervosa - Main portion of posterior lobe, containing Herring bodies of axons
2. Infundibulum - the connecting stalk carrying tracts from the hypothalamus
What artery supplies mainly the pars nervosa?
Inferior hypophyseal arteries, which are branches of the internal carotids. They give rise to fenestrated capillaries which drain into hypophyseal veins.
What are the superior hypophyseal arteries?
Branches of the internal carotids and circle of willis which supply the hypophyseal portal system.
How does the hypophyseal portal system blood work?
1. Superior hypophyseal arteries supply the median eminence and infundibulum, forming a capillary plexus which drains into portal veins.
2. Portal veins carry major blood supply to anterior lobe, which has no direct arterial supply except a few possible indirect branches from superior and inferior hypophyseal arteries.
3. Secondary capillary plexus in pars distalis has wide sinusoids with fenestrated endothelium for more exchange.
What is the venous drainage of the pituitary?
Pars distalis and pars nervosa both drain via hypophyseal veins which empty into cavernous sinus.
What nuclei supply tracts to the pars nervosa?
Supraoptic and paraventricular nuclei of hypothalamus. Their fibers mostly end in pars nervosa, but some terminate in the infundibular stalk
What nuclei supplies the infundibular stalk to control the adenohypophysis (via portal system)?
Tuberal nuclei - produce releasing factors which are carried to adenohypophysis via the portal vessels
What is the pars distalis and what cell types make it up?
Cells which comprise about 75% of the pituitary, part of the adenohypophysis. It has cords of cells separated by fenestrated capillaries with wide lumina.
Cell types: acidophils (most abundant ~70%), basophils (slightly less abundant ~30%), a few chromophobes
What are chromophobes?
Inactive or depleted cells of the pars distalis, Name means "afraid of color", they contain few granules.
Where are the hormones that act on pars distalis cells released?
Released by hypothalamic tuberal neurons by their axon terminals into the median eminence. These factors enter the capillary plexis here and travel to the secondary capillary plexus through hypophyseal portal veins
Can be releasing factors or inhibiting factors.
What are the two types of acidophils?
1. Somatotrope (~50% of adenohypophysis)
2. Lactotrope / Mammotrope (~20% of adenohypophysis)
What are the three types of basophils?
1. Thyrotrope (~5%)
2. Gonadotrope (~10%)
3. Corticotrope (~15%)
What hormones do somatotropes produce and what are their hypothalamic regulators?
They are acidophils which produce growth hormone / somatotropin, which stimulate growth via IGF-1.
Upregulation: GHRH - Growth hormone releasing hormone
What hormones do lactotropes / mammotropes produce and what are their hypothalamic regulators?
They are acidophils which produce prolactin (PRL) - mammary gland development + production of milk
Upregulation: TRH - Thyrotropin releasing hormone
Downregulation: Dopamine (this is usually on)
What hormones do thyrotropes produce and what are their hypothalamic regulators?
They are basophils which produce thyroid-stimulating hormone (TSH)
Upregulation: TRH - thyrotropin releasing hormone (same as lactotropes / mammotropes)
What hormones do gonadotropes produce and what are their hypothalamic regulators?
They are basophils which produce FSH and LH which stimulates follicle development in ovary and spermatogenesis in testes
Upregulation: GnRH - gonadotropin releasing hormone
What hormones do corticotropes produce and what are their hypothalamic regulators?
They are basophils which produces proopiomelanocortin which is cleaved into adrenocorticotropic hormone (ACTH) and beta-lipotrophic hormones, stimulating release of glucocorticoids + gonadocorticoids in adrenal cortex
Upregulation: CRH - Corticotropin-releasing hormone
How can the specific cell type of acidophil vs basophil be determined in the pars distalis?
Within each class, you need to use immunohistochemistry
What is the pars intermedia?
Poorly developed portion of adenohypophysis in humans, which may be a remnant of Rathke's pouch during development.
It contains colloid-filled cysts, chromophobes, and basophils.
What is the neurohypophysis technically?
Just a neurosecretory site for neurons whose cell bodies are in the supraoptic and paraventricular nuclei of the hypothalamus.
What is the major cell type of the neurohypophysis?
Pituicytes - they are glial cells which resemble astrocytic neuroganglia
What are the nerve fibers and terminals of the hypothalamo-hypophyseal tract that contain neurosecretory material?
Herring bodies - dilations in the axons which are visible by LM
-They also often contain lipofuscin pigments
What is a neurophysin?
They are carrier proteins for Oxytocin or ADH (two different types). Oxytocin and ADH are packaged by neuronal vessels along with a specific neurophysin and ATP. The neurophysin is cleaved en route to the Herring body.
Is each neuron specific to oxytocin / vasopressin or are they produced by the same one?
There are separate populations of neurons in the supraoptic / paraventricular nuclei that produce each hormone
What two hormones are released by the neurohypophysis?
2. ADH (antiduretic hormone) / vasopressin
What is oxytocin, its target, and its trigger?
Produced by neurosecretory cells along with neurophysis.
Target: Uterine smooth muscle, mammary gland myoepithelial cells
Trigger: Neural stimuli to hypothalamus
What is ADH / vasopressin?
Produced by neurosecretory cells, along with it's neurophysin
Target: Distal tubules and collecting ducts of kidney for increased water resportion
Trigger: Increase in plasma osmolality / decrease in blood volume
What is the pineal gland?
It is the dorsal extension from the posterior part of the roof of the diencephalon. Its lumen is obliterated as walls thicken with age, and it remains attached to the roof of the third ventricle.
How does the pia mater relate to the pineal gland?
It is continuous with capsular connective tissue, which extends into the gland as thick septae + thinner trabeculae
What are the two main cell types of the pineal gland?
Pinealocytes - relatively large cells with deeply creased nuclei and prominent nucleoli. Has long cytoplasmic processes with club-shaped terminations
Glial cells - less numerous (5%), they form the supporting network associated with blood capillaries. They also have long cytoplasmic processes are are hard to differentiate from pinealocytes
What are the corpora arenacea? Why is this useful?
Also called the brain sand, they are darkenings which are concretions of calcium phosphate salts in the pineal gland that increase with age. They are located in areas of glia and stromal connective tissue, and make the pineal gland a good radiological landmark
What is the function of the pineal gland?
Pinealocytes produce serotonin and melatonin, among others. Correct regulation may play a role in seasonal affective disorder
- Role in gonadal function, since tumors destroying it are associated with early-onset puberty
-Melatonin - for adjusting to day-length. May play a role in jet lag
-Serotonin - happiness neurostransmitter
What is the function of the stroma of the thyroid gland?
It is a delicate CT covering which forms a thin capsule extending into the gland, dividing it into lobules
How is the thyroid gland organized?
Arranged into spherical follicles ranging in size up to 1mm in diameter. A network of fenestrated capillaries surrounds each follicle.
What is inside and immediately around each thyroid follicle?
The lumen is filled with colloid, the stored secretory product of follicular cells. Lined with simple cuboidal epithelium resting on basement membrane.
What is the blood supply and drainage of the thyroid gland?
Mostly supplied by the superior and inferior thyroid arteries. The veins in the gland form a rich plexus, and it has good thyroid drainage
What are thyroid follicular cells and what makes them unique?
They are simple cuboidal epithelium with heights that very with activity. The epithelium rests on a basement membrane surrounded by fenestrated capillaries. They produce thyroxin (T4) and triiodothyronine (T3).
Unique: Only endocrine cells that provide extracellular storage of secretory product
What sits in the lumen of follicular cells?
Thyroidal colloid. This is iodinated thyroglobulin. The concentration of I- is about 30-fold higher than in blood by means of ATP-dependent iodide transporters which transcytose iodide from blood to the colloid.
What is thyroglobulin? Where is it modified prior to the lumen?
The protein made mostly of tyrosine dimers which dilates the rough ER of follicular cells. When iodinated, it will be the thyroidal colloid.
1. Rough ER - synthesizes thyroglobulin polypeptides, adds glucosamine and mannose
2. Golgi - condenses it, adds galactose, fucose, and mannose
What is packaged in the Golgi with thyroglobulin? What is its function?
Thyroid peroxidase - sits on apical membrane after exocytosis and oxidizes iodide (I-) to free iodide (I2). Also facilitates the iodination of thyroglobulin
How does iodine associate with thyroglobulin?
It is coupled to tyrosine groups in thyroglobulin, forming mono-iodothyronine (MIT) and di-iodothyronine (DIT). This is facilitated by thyroid peroxidase in the lumen of thyroid follicles
How are T3 and T4 formed?
First, the iodinated thyroglobulin is taken up from the follicle into the follicular cells by endocytosis. This endosome will have contents cleaved by lysosomal enzymes. MIT and DIT from within colloid (iodinated thyroglobulin) will couple. MIT + DIT = T3. DIT + DIT = T4.
How are T3 and T4 transported? What happens to MIT and DIT and T2?
MIT / DIT / T2 (from 2 MIT coupling) are all recycled.
T3 and T4 are released into the blood for transport by serum carrier proteins.
How much T3 / T4 are produced. What is their relative action and stability?
T4 : T3 = 20:1 ratio. T3 is 5 times more active, and is generated from T4 in kidney, liver, and heart. T3 is short-lived and cannot be transported far. T4 is long-lived and can be cleaved to T3 for more action at the specific target
What is the function of T3 / T4?
They regulate the basal metabolism of carbohydrates, proteins, and fats. Thus, heat production, body and tissue growth, and development.
What is the function of TSH? What is the negative feedback?
Controls all stages of T3 and T4 synthesis, especially uptake of colloid into follicular cells by endocytosis, and release of T3 / T4.
Elevated T3 / T4 levels are negative feedback to TRH released by tuberal neurons.
Where are parafollicular cells found and what do they look like with staining? What is the big identifier?
They are large and stain poorly with H&E. They can be attached to the basement membranes of thyroid follicles but they do not contact the lumen of the follicles. They can be beneath the follicular cells or in small cluster in the interstitium between follicles.
Identifier: Contain secretory granules (calcitonin) in close proximity to surround capillaries, do not have enlarged rough ERs
What is the function of parafollicular cells?
They produce calcitonin, which functions to decrease blood calcium levels by directly binding osteoclasts and shutting them down. Increases renal and intestinal Ca+2 excretion as well.
What is the morphology of the parathyroid glands? What changes as you age?
They are surrounded by a delicate connective tissue capsule extending incomplete trabeculae into the gland. Cells are arranged in clumps with rich vascular network. There are many adipocytes - fat cells and connective tissue increase with age.
Where are the parathyroid glands and what is their function?
They are two glands on the dorsal surface of each thyroid lobe (4 total), about the size of a pea.
Function: release parathyroid hormone, which stimulates release of Ca+2 from bone and renal / intestinal calcium resorption. This is essential for life.
What are the principal / chief cells of the parathyroid gland?
Relatively small cells with large nuclei and a few small secretory glands. They produce parathyroid hormone (PTH)
What are oxyphil cells?
Cells of the parathyroid appearing at 4-7 years and increase with age. They are larger, acidophilic cells due to their many mitochondria. They also have smaller nuclei.
-May be derived from aged chief cells
-Function is largely unknown, but may release PTH
What structurally makes up the suprarenal / adrenal glands?
They are crescent-shaped paired organs atop the cranial pole of each kidney.
Each gland consists of two separate endocrine organs:
1. Adrenal cortex
2. Adrenal medulla
Connective tissue stroma forms a delicate capsule which extends into the cortex as trabeculae, with many reticular fibers
What are the three types of arteries that supply the adrenal glands?
1. Capsular - coursing around the outside
2. Cortical - give rise to capillaries in the cortex (bring deoxygenated blood to the medulla which holds hormones)
3. Medullary - arterioles which course through the cortex and form capillary network in the medulla
What is the venous drainage from the medullary cortex?
There are no veins in the adrenal cortex - venous return begins at the cortico-medullary junction where cortical capillaries containing hormone-rich but oxygen-poor blood anastomose with capillaries from medullary arterioles to form thin-walled venous blood to supply the medulla.
What are the three zones of glandular cells of the adrenal cortex?
1. Zona glomerulosa - outer (10-15%)
2. Zona fasciculata - middle (60-80%)
3. Zona reticularis - inner / nearest medulla (5-7%)
What is the zona glomerulosa? What does it do? Is it ACTH-dependent or independent?
Outermost layer of adrenal cortex
-Rounded cell clumps close to fenestrated capillaries
-Produces aldosterone, mineralcorticoid increasing sodium uptake in kidney
What produces aldosterone and how is it produced by the cells that make it?
Produced by zona glomerulosa cells in an ACTH-independent fashion. These cells have lipid droplets and mitochondria with conventional cristae (despite aldosterone being a steroid).
Cholesterol is uptaken by receptor-mediated endocytosis of LDLs, modified by hydroxylation reactions. The growing hormone shuttles between sER and mitochondria which both have synthetic enzymes
What is the zona fasciculata? What does it do? Is it ACTH-dependent or independent?
Middle zone of adrenal cortex
-Cells are in straight cords / columns which run radially
-Produce glucocorticoids - mainly cortisol, which functions to promote metabolism and suppress inflammatory response
-ACTH dependent zone
What produces cortisol and how is it produced by the cells that make it?
Zona fasciculata cells in an ACTH-dependent fashion. Have many lipid droplets, and mitochondria with tubulovesicular cristae. Most of cytoplasm is sER. These 3 components function together to make glucocorticoids like cortisol.
What is the zona reticularis? What does it do? Is it ACTH-dependent or independent?
Inner zone of adrenal cortex
-Cells are smaller and darker, with few lipid droplets and more lipofuscin.
-Produces gonadocorticoids, mostly dehydroepiandosterone
What produces dehydroepiandosterone?
Zone reticularis of adrenal cortex, in an ACTH-dependent fashion
What is the adrenal medulla? What are the cells actually?
Inside layer of suprarenal glands, it borders the zona reticularis. Cells are polyhedral, surrounded by capillaries and cortical veins.
Cells are actually modified postganglionic sympathetic neurons, part of the chromaffin system of cells of the sympathetic nervous system. They stain with dichromate salts
What are chromogranins? What is needed to package them in the cells?
They are the proteins of the adrenal medulla which complex with the catecholamines in membrane-bound secretory granules, much like neurophysins. These cells exhibit prominent Golgi apparatuses to package these with epi and nor-epi
What are the relative concentrations of catecholamines produced by the adrenal medulla?
Epinephrine - 80%
Norepinephrine - 20%
Produced by separate cell populates, and complexed in secretory granules with chromogranins
How does the storage of products differ between the adrenal cortex and adrenal medulla?
Adrenal cortex does not store in vesicles, it releases it immediately
Adrenal medulla stores the products in membrane-bound vesicles
What is the function of glucocorticoids from the adrenal cortex acting on the adrenal medulla?
i.e. cortisol. It induces the synthesis of PNMT to convert norepinephrine to epinephrine. Glucocorticoids also suppress axon formation in adrenal medullary cells during development
How is norepinephrine converted to epinephrine?
Certain chromaffin cells of the adrenal medulla synthesize phenylethanolamine N-methyltransferase (PNMT), which is induced by glucocorticoids from zona fasciculata
What is hypoadrenocorticism?
Addison's disease - destruction of adrenal cortex often because of tuberculosis. Leads to weakness, weight loss, and low blood pressure (no aldosterone). Increased secretion of ACTH due to no negative feedback leads to skin pigmentation
What is hyperadrenocorticism?
Cushing's syndrome - can be caused by tumor on pituitary leading to increased ACTH secretion. It is increased adrenal cortex activity leading to obesity, hirsutism (male-like hair growth), moon face, thinning of skin, and lipodystrophy (fat storage problems)