Lecture 36 Flashcards
Endocrine - general concept
Endocrine cells secrete products into circulation (fenestrated capillaries). Most are hormones used to communicate across diff systems in the body
Many hormones made, but they don’t know where to go
Target cells have specific receptors that respond to those specific hormones. So the sorting occurs at the target; this is mediated by cell surface or nuclei receptors.
Target cells at distant sites are affected by receptor-mediated signaling
2 types of endocrine hormones and 2 mechanisms
- Requires intracellular secondary messengers to evoke physiological response
- PROTEIN HORMONE binds to TRANSMEMBRANE RECEPTOR on target cell
- this causes conformational change where accessory proteins can bind and cause physiological response - Membrane diffusible hormone binds to nuclear receptors affecting gene transcription
- STEROID HORMONE often bound to
CARRIER PROTEIN
- steroid hormone is lipid soluble, so it is carried through bloodstream and delivered to target cell
- steroid hormone enters nucleus of cell, causing changes in gene transcription
Organs with endocrine cells
Endocrine cells distributed throughout body
- islets of Langerhans in pancreas (pancreas makes enzymes and hormones)
- ovaries
- testes
Major endocrine organs
Function is to make hormones
- pituitary gland in brain
- pineal gland in brain
- thyroid gland
- parathyroid gland
- adrenal gland
Adrenal gland - basics and hormones
Adrenal gland is on top of kidney. It is a major endocrine organs. Mass of endocrine cells organized. Folded structure looks quite symmetrical
H and E: outer cortex is lighter than inner medulla
Adrenal gland has cortex on outside and medulla on inside
Adrenal gland makes diff products, and the names indicate location
Hormones made in cortex:
- Mineralocorticoid Hormones
- associated with absorption of minerals from kidney - Glucocorticoid Hormones
- associated with glucose metabolism - Gonadocorticoid Androgens
- influence activity of reproductive system
Hormones made in medulla:
- Catecholamine Epinephrine
- Catecholamine Norepinephrine
Adrenal gland layers
Medulla
Inner to outer (all 3 are in cortex):
- Zona reticularis: network of cells that is profused by a lot of sinusoids
- Zona fasciculata: cells that form fascicles, makes up 70% of adrenal gland
- Zona glomerulosa: has cells that form glomeruli
Outside of cortex has CT capsule with lots of collagen inside
Blood pathway in adrenal gland
All blood delivered to adrenal gland comes from SUPRARENAL ARTERY, which is found in capsule outside. Suprarenal artery branches into arterioles and capillary networks that enter cortex (ADRENO-CORTICAL SINUSOID). Then, it delivers blood through thin wall capillaries into the medulla where there are large CENTRAL ADRENO-MEDULLARY VEINS that collect all the blood.
Capillary networks collect products from cells that line next to the capillaries and sinusoids
In addition to these capillary networks, the medulla has a separate blood supply that brings in oxygen-rich blood directly into the medulla via a MEDULLARY ARTERIOLE
- The cortex removes a lot of nutrients and oxygen already.
- So to supply the medulla with oxygen and nutrient-rich blood, there is the arteriole venus shunt that carries blood directly into the medulla
All blood leaves through large veins
All cells in adrenal cortex are regulated by….
All cells in adrenal cortex are regulated by ACTH (adrenal cortical trophic hormone), which comes from pituitary gland.
Zona glomerulosa - regulation and products
Regulated by ACTH (stimulates production of aldosterone) and angiotensin II
Zona glomerulosa makes mineralocorticoid. Aldosterone is a mineralocorticoid.
Aldosterone influences DCT in kidney to increase sodium chloride absorption.
Zona fasciculata - regulation and products
Regulated by ACTH.
Zona fasciculata makes:
- Glucocorticoids
- cortisol (stress hormone, but also liberates sugar from the liver, involved in glucose metabolism)
- corticosterone
- Gonadocorticoids
- DHEA (androgen)
- DHEAS (androgen)
- androstenedione
Zona reticularis - regulation and products
Regulated by ACTH.
Zona reticularis makes:
- Gonadocorticoids
- DHEA (androgen)
- DHEAS (androgen)
- androstenedione
- Glucocorticoids
- cortisol (stress hormone, but also liberates sugar from the liver, involved in glucose metabolism)
- corticosterone
Androgens
Made by zona fasciculata and zona reticularis.
Androgens are testosterone pre-cursors. Androgens have very different functions in the body.
Both male and female get testosterone made by adrenal gland. But males have another source of testosterone in their testes.
The ovaries also make androgens, but they are immediately changed into estrogen.
Adrenal medulla - regulation and products
Regulated by sympathetic neurons.
It is a derivative of the neurosystem
- neural crest cells migrate into the adrenal gland and form the medulla
Adrenal medulla makes:
- catecholamines
- epinephrine
- norepinephrine
Zona glomerulosa - H and E appearance and how it produces its content
- cells form circular arrangements, but they are not acini. They secrete into capillaries at the basal end of the cell
- a lot of cells contain inclusions, specifically lipid droplets that contain cholesterol
- lipid droplets, mitochondria, smooth ER
- adrenal gland cortex produces steroid hormones and the precursor of steroid hormones is cholesterol (lipid).
- use lipids stored in enzyme systems to make the steroid hormone
- the steroid hormone made is aldosterone
- Secretes Aldosterone in response to Angiotensin II
- aldosterone increases absorption of sodium chloride in DCT and ascending limb of the loop of henle in renal tubules
- cells need lots of mitochondria to do this
- the enzymes that make the steroid hormones are located in smooth ER and mitochondria
Zona fasciculata - H and E appearance and content
- cells make elongated fasicles and can see capillaries surrounding the secretory cells
- has lipid droplets, mitochondria with tubular cristae, smooth ER
- Secretes Cortisol in response to Adrenocorticotropic Hormone (ACTH)
- Cortisol promotes glucose secretion from hepatocytes
- Cortisol suppresses inflammatory responses
Zona reticularis - H and E appearance and content
- next to adrenal medulla
- cells form loose network that is surrounded by sinusoids
- has lipid droplets, mitochondria, smooth ER, lysozymes, secretory vesicles
- Cells secrete Androgens in response to Adrenocorticotropic Hormone (ACTH)
- Primary source of male sex hormones in females
Adrenal medulla - H and E appearance, EM appearance and content
- made by meshwork of cells profused by many sinusoids
- in EM, the cells have lots of dark secretory vescicles
- Cells contain abundant membrane-bound granules
Adrenal medulla - hormones made
Adrenal medulla makes protein hormones, they do not make steroid hormones
Secretions stimulated by nervous system
These cells are modified post-ganglionic neurons, innervated and have lots of secretory granules inside
- 20% of chromaffin cells secrete Norepinephrine
- 80% of chromaffin cells secrete Epinephrine
With EM, ppl can distinguish which cell makes norepinephrine and which
cells makes epinephrine, by the size and location of these secretory vescicles or granules.
Pathway of epinephrine and norepinephrine production
Chromaffin cells of adrenal medulla makes epinephrine and norepinephrine. Chromaffin cells are modified sympathetic postganglionic neurons derived from neural crest
- Chromaffin cells are innervated at bottom, which stimulates the cell
- Use tyrosine to make DOPA to make dopamine to make norepinephrine
- To make epinephrine from norepinephrine, the cells needs PNMT enzymes. PNMT needs glucocorticoid hormones. Glucocorticoid hormones come from the zona reticularis, and they travel down sinusoids to the adrenal medulla to induce the enzymes to change norepinephrine to epinephrine.
- Glucocorticoids required for methylation of norepinephrine to form epinephrine - Epinephrine and norepinephrine are bound to carrier proteins called chromogranins, which are stained with chromium salts. Together, the hormones are released into blood stream
- b/c of chromogranins, the cells are called chromaffin cells, which have affinity for chromium salts
- if you use stain containing chromium salts, those cells pick it up
Norepinephrine and epinephrine functions
Both norepinephrine and epinephrine are hormones for fight or flight reaction. Diff targets have diff affinities for epinephrine or
norepinephrine. There are slight diff in the way they work
Thyroid and parathyroid location and composition
Both located above larynx, both make different types of hormones
Under thyroid gland are small structures associated with the thyroid gland but are independent; these are parathyroid glands
Both thyroid gland and parathyroid glands are endocrine glands, but thyroid gland or cells in thyroid gland have exocrine component to hormone production
Parathyroid gland is located behind thyroid gland
Thyroid - appearance in body and in H and E
- shaped like butterfly
- profuses through veins and arterioles
- thyroid has endocrine and exocrine components to hormone production
- the exocrine form of thyroid hormone makes the cells form THYROID FOLLICLES
- follicles have diff sizes depending on activity of ep cells
- many CAPILLARIES surround the thyroid follicles
- in thyroid gland, FOLLICULAR EPITHELIAL cells secrete THYROGLOBULIN stored as COLLOID in the thyroid follicles
- Easiest organ to identify: contains highly eosinophilic material (colloid) surrounded by a simple cuboidal epithelium (follicular ep)
- Staining with PAS, can see colloid that stains magenta. Colloid is a glycoprotein that makes up the content of the thyroid follicles.
Hormones made by thyroid gland
- makes thyroid hormones T3 and T4
- makes calcitonin hormone
Production of thyroid hormones by thyroid gland
- thyroid hormone contains 2 diff components: chain of aa and iodine (which we get from drinking water)
- scientific name of thyroid hormone is iodinated thyroglobulin, which is stored in colloid within thyroid follicle
- Pumps transport iodide across basal membrane (needs energy via mitochondria) and iodide concentrates within colloid
- Secretion of thyroglobulin (protein made mostly by tyrosine molecules) into colloid. Thyroid peroxidase stays at cell surface bc it is transmembrane protein that gets stuck to apical cell surface where it will then iodinate thyroglobulin
- thyroglobulin is protein made in ER, glycoxylated in golgi apparatus and packaged in secretory vesicles to be delivered to apical end of the ep cells - Iodination of Thyroglobulin at the cell membrane by thyroid peroxidase. This is oxidation process.
- Proteolysis of iodothyroglobulin after ‘uptake of colloid droplets and fusion with lysosomes’
- when cell needs to make thyroid hormone, it picks up the iodinated thyroglobulin, forms lysozomes and there are enzymes in the cells that break up the thyroglobulin into 2 parts: T3 and T4 - Release of triiodotyrosine (T3) and thyroxine (T4) into the circulation
- depends on how many tyrosine parts are iodinated
- T3 means 3 tyrosine residues are iodinated
- T4 means 4 tyrosine residues are iodinated
- both T3 and T4 delivered into blood stream via endocrine fashion
- T4 is more abundant but not as potent as T3
- in most target organs of thyroid hormone, T4 will be converted to T3
Lots of components in cells have a thyroid response element. It controls general cellular metabolism. W/o sufficient thyroid hormone,
our cells don’t metabolize stuff well, and there are diseases and conditions related to that, with dire consequences
TSH
Thyroid hormone production is regulated by thyroid stimulating hormone (TSH), which comes from the pituitary gland
TSH binds to receptors on thyroid ep cells, which get activated to iodinate thyroglobulin, and make T3 and T4.
If you make enough T3 and T4, it shuts down the production of TSH from pituitary gland: feedback loop
Graves’ disease
Produce anti-TSH receptor antibodies, which are against TSH receptor.
This antibody does not block receptor but stimulates. The thyroid ep cells think they are stimulated by TSH, and they produce a lot of thyroid hormone.
The pituitary gland shuts down because it sees a lot of thyroid hormone and thinks it does not need to put out TSH anymore.
As a result, there are a lot of thyroid hormones floating in Graves’ disease, making them waste away. Their cellular metabolism is very increased.
Parafollicular cells
Parafollicular cells, also called C cells, are neuroendocrine cells in the thyroid
- this cell type is located outside of thyroid follicle
- large nuclei surrounded by capillaries that are not part of thyroid follicle but sit in CT in b/w thyroid follicles
- large cell with many secretory granules
- secrete Calcitonin, lowering blood calcium levels
Calcitonin
- one main target of calcitonin is the osteoclast
- osteoclasts resorb bone
- bone stores lots of calcium and to lower amount of calcium in blood, need to quiet down osteoclasts
- Parafollicular cells secrete calcitonin, which binds to receptors on osteoclast and inhibits bone resorption
- The number of osteoclasts actively resorbing bone and releasing calcium into the circulation is regulated by Calcitonin and Parathyroid Hormone
- Calcitonin acts to decrease blood calcium levels
- Calcitonin does not act on kidneys!!
Parathyroid hormone
Parathyroid Hormone activates osteoclasts. Parathyroid hormone acts to increase blood calcium levels
Parathyroid gland
- beneath thyroid gland
- parathyroid gland looks like lymph node and has lots of tiny nuclei, not much
cytoplasm - cells in parathyroid gland are chief cells aka principal cells that make parathyroid hormone
The Parathyroid Gland contains 2 main epithelial cell types:
- Cluster of chief cells secreting parathyroid hormone
- Cluster of oxyphil cells that have highly eosinophilic cytoplasm
- presence of oxyphil cells amongst chief cells is a clue that you are looking of parathyroid gland
- Oxyphil cells contain abundant mitochondria. They have no known secretory function.
- they have lots of cytoplasm, is large cell, eosinophilic cytoplasm, central nucleus
- lots of mitochondria in cell makes it eosinophilic
Parathyroid Hormone (PTH)
PTH binds to receptors on osteoclasts. Calcium will be released or mobilized
Bone:
Stimulates osteoclast differentiation and bone resorption.
Kidney:
Stimulates calcium re-absorption in proximal convoluted tubules.
Gut:
Stimulates synthesis of vitamin D, necessary for intestinal calcium uptake.
