Endocrine System Flashcards
Arnold Adolph Bertold
1849 conducted the first formal study of endocrinology
Professor at Gottingen University
The effect of castration on the development of male phenotype:
Observation 1: Removal of testes leads to the development of female like phenotype (capon)
Observation 2: Transplanted testes supported the development of male phenotype. This effect could not be mediated by nerves, which were cut.
Conclusion: Therefore, Berhold postulated existence of a substance that travels through the bloodstream to target organs (hormones/ testosterone)
Caponization: development of female phenotype, makes meat taste better
Hormone definition: What it is?
A signaling molecule released by a cell and conveyed by the blood stream, by neural axons, or by local diffusion to cells in target tissues.
Hormone definition: What is its chemical nature?
Protein, peptide, catecholamine, steroid or iodinated tyrosine derivative
Hormone definition: What does it do to target tissue?
Regulates existing metabolic pathways (through second messengers) or regulates synthesis of enzymes and other proteins at the DNA level. In this way, it regulates the rates of specific reactions without itself contributing energy or initiating the process
metabolism
sum of all chemical reactions in cell
Main endocrine glands
Pituitary gland, hypothalamus, pineal gland, Thyroid gland, parathyroid glands, adrenal gland, kidney, gut, ovary, testis, placenta, pancreas, liver, heart,
Hypothalamus interactions with pituitary gland.
Pineal gland located in diencephalon
Heart has cells that secrete hormones
GI system secretes more than 40 types of hormones
endocrine secretion
hormone releasing cells secrete hormones into the internal environment (interstitial fluid)
exocrine cells secrete products outside into ducts
endocrine cells
cells that release hormones are therefore called endocrine cells
endocrine glands
endocrine cells can be either scatter through tissues, or they are parts of specialized _______
endocrine system
the collection of endocrine glands a other endocrine cells forms the endocrine system
endocrinology
sub-discipline of physiology that studies the endocrine system
Functions of the endocrine system
To regulate metabolism, fluid status, growth, sexual development, reproduction
The endocrine and nervous systems work together to maintain homeostasis
autocrine
hormone acts on the cell which released it
Paracrine
hormone acts on adjacent cells without entering the blood stream
Endocrine
before reaching target cells, hormone first enters the blood stream
neurocrine
hormone secreted by neurons, inconsistent use of the term
neuroendocrine
the interaction between neurons and endocrine cells
distance to closest capillary
50 to 100 microns away, thinner than human hair
4 categories of hormones
- peptide, protein , and glycoprotein hormones
- Catecholamine hormones
- Thyroid hormones
- Steroid hormones
- Lipokines? new category
Peptide and protein hormones
eg: peptides; vasopresin, oxytocin, glucagon
proteins; insulin, growth hormone, prolactin
Synthesis: DNA, mRNA, preprohormone, prohormone, hormone
Storage: stored in secretory granules originating from Golgi apparatus
Secretion: secreted by exocytosis
catecholamine hormones
eg. epinepherine, norepinephrine, dopamine
Synthesized form the amino acid tyrosine
Stored in secretory granules in the cells that synthesize them
Released by exocytosis
Also work as neurotransmitters
Thyroid hormones
eg. thyroxine (T4), triiodothyronine (T3)
Synthesized from tyrosine and iodide
Stored extracellularly in follicles of thyroid gland as a component of a large protein molecule
Secretion requires retrieval from follicle and enzymatic release from the storage protein
Are lipophilic, transported in plasma where they are bond to carrier proteins.
Although they are lipophilic, they are charged and require transporters to cross membrane
Steroid hormones
eg. cortisol, aldosterone, androgens, vitamin D
Synthesized from cholesterol
Not stored in the gland of origin or elsewhere, the increase of secretion achieved by mobilizing the synthesis from cholesterol
Are lipophilic, transported in plasma where they are bond to carrier proteins
Cortisol has mineralocorticoid activity.
Aldosterone has glucocorticoid activity.
negative feedback
hormone secretion controlled by negative feedback. Dominant mechanism of regulating hormone secretion and release.
Processes controlled by negative feedback are common, stable, critical for the maintenance of homeostasis.
The result of the process “feeds back” into the process to stop it. Can inhibit further hormone secretion from endocrine cells.
Could be a long or short loop.
Positive feedback
rare and controls surges of hormones
The out come of the process “feeds back” to the process to produce more of the same outcome. Target cells produce a product which further stimulates endocrine cell to secrete more hormone.
Processes controlled by the positive feedback are rare unstable, used when a surge of hormone is required, such as the luteinizing hormone surge before ovulation
Hormone turnover
After secretion into the extracellular fluid, hormones circulate either free or bound to other plasma constituents.
Eventually, hormones are taken up by cells and are metabolically degraded, or removed by urinary or biliary secretion.
hormone half-life time`
t1/2, the time during which the hormone loses 50% of its biological activity, varies between hormones. Peptides/ proteins from minutes to tens of minutes (eg ~15 days for Vitamin D)
Cellular events triggered by hormones
- Hormone binds to a specific receptor in the target cell. (The target cells are sub-populations of cells that are programmed to express receptors for the given hormone)
- This initiates intracellular events leading to the final physiologic effect.
- Specifically, the receptor activation triggers changes in enzyme activity or concentration, leading to the regulation of multiple metabolic pathways and eventually to changes detectable at the level of cell and whole organism
The hormone concentration together with the number and sensitivity of involved receptors determine the magnitude of the hormone effect
Change enzyme activity or concentration
Hormone actions on target cells
- Water soluble (and lipophobic) hormones bind to receptors located in the target cell membrane. This either directly or vie second messengers, regulates activity of existing enzymes. Fast. Uses signal cascade
- Water insoluble (and lipophilic) hormones bind to nuclear receptors, to regulate the gene transcription and/ the synthesis of new enzymes or structural proteins. Slow
Number of receptors on a single cell
2,000 to more than 100,000
Action of catecholamine and polypeptide hormone action
many activate either cAMP or IP3/DG as second messengers
Second messengers activate protein kinases and these phosphorylate (activate) other proteins, leading to the eventual physiologic effect.
Hormones are considered the first messenger.
cAMp messenger system
cAMP activates protein kinase A (PKA), which in turn activates other enzymes by phosphorylating them
Besides phosphorylating existing enzymes, PKA can alter gene expression via CREB- CRE pathway in the nucleus
Some hormones can both inhibit and stimulate the adenylate cyclase. For instance, epinephrine stimulates cAMP in cells that express beta 2 receptor, but it inhibits cAMP in cells that express alpha 2 receptor
In some cases, tow hormones can regulate the same cascade. Glucagon can stimulate cAMP and insulin stimulates its breakdown
One hormone can stimulate adenylate cyclase in some cells and inhibit adenylate cyclase in other cells
Ca diacylglycerol messenger system
regulate protein activation and/or phosphorylation
G protein couples to phospholipase C, Diacylglycerol can regulate phospholipase C, calcium is third messenger, cofactor in activation of enzymes or bind to calmodulin to form complex and activate CaCaM protein kinase
Ca is low concentration in ICF, IPC triggers release of calcium from ER
Ca is derived from both external and internal sources at the cellular level
amplification
the plasma concentration of hormones is very low (pmol or nmol/L) and only a few molecules reach each target cell. Intracellular signal amplification allows small number of signaling molecules to elicit physiologic response.
a single ligand (hormone) activates multiple G proteins and each of these activates an enzyme that produces multiple molecules of the second messengers, activate other enzymes, and these other enzymes catalyze reactions on multiple molecules of the substrate
Mechanisms of steroid and thyroid hormone action
In addition to nuclear receptors, steroids can have receptors also in cell membrane
Steroid and thyroid hormones regulate about 1% of all genes in target cells.
Products: enzymes, structural proteins, receptor proteins, transcriptional proteins
Thyroid hormones still need transporter to get inside the cell
synergism of hormonal action
in some instances, different types of hormones work together (eg. steroids increase the synthesis of enzymes which are regulated by catecholamines/polypeptides)
gluconeogenesis
cortisol increases synthesis of hepatic gluconeogenic enzymes
These enzymes are stimulated by epinephrine and/or glucagon
Hypothalamic-pituitary system
hypothalamus controls,
pituitary releases hormones that control
Target endocrine and non-endocrine tissues
Helps to control processes that are independent of other endocrine glands
Thalamus, epithalamus and hypothalamus
lateral walls of Third ventricle in the middle
Median eminence is rotated 90 degrees/distorted.
Pars tuberalis wraps around pituitary stalk
anterior lobe
pars distalis, adenohypophysis, originates from ectoderm of oral cavity called Rathke’s pouch
darker staining on histology
Cells are controlled by hypothalamic releasing hormones (RH) and inhibiting hormones (IH). These are brought from hypothalamus by portal vessels
In response to RH and IH, anterior lobe releases tropic hormones which regulate hormone secretion in other glands (FSH, LH, TSH, ACTH) and other hormones that control metabolism in non-endocrine tissues (GH, PRL, MSH)
posterior lobe
neurohypophysis, neural tube,
originates from neural tissue
Surrounded by darkly staining pars intermedia
Hypothalamic-pituitary system controls endocrine glands and non-endocrine tissues
mediator between nervous and endocrine control systems
Secretes two categories of hormones:
1. Hormones that are transported via axons to and released in the posterior pituitary
2. the release and inhibiting hormones that are released in the hypothalamus, reach the anterior pituitary via portal vessels and regulate activity of anterior pituitary endocrine cells
Capillary beds in median eminence travel through pituitary stock and has 2 beds in series connected by portal vein. Connects the beds between hypothalamus and anterior pituitary
Posterior pituitary does not have endocrine cell bodies but the anterior pituitary does so the anterior pituitary has the glands to synthesize and secrete hormones
Neurons are endocrine cells secreting hormones in posterior pituitary
Another set of neurons terminate in median eminence and release, hormones in capillaries in median eminence to travel to anterior pituitary. These include release hormones that stimulate secretion in anterior pituitary or inhibitory hormones to inhibit secretion in anterior pituitary
hypothalamic hormones released in pituitary
(2), oxytocin and antidiuretic hormone (ADH)
true pituitary hormones
(7)
Control other glands: Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), thyrotropin (TSH)
Adrenocorticotropin (ACTH)
(FSH and LH are Gonadotropins)
Control non endocrine tissues: Prolactin (PRL), Somatotropin (GH), Melanotropin (MSH)
vasopressin
antidiuretic hormone (ADH), water metabolism, increases water reabsorption,
nanopeptide, secreted by posterior pituitary
inhibits diuresis and controls blood volume and pressure
oxytocin primary function
Lactation, milk secretion and uterine contractions
prolactin
PRL, lactation, milk secretion and uterine contractions
“mother love hormone”, causes stimulation of maternal behavior and pair bonding
melanotropin
skin pigmentation, melanocyte stimulating hormone, MSH, stimulates melanogenesis,
Polypeptide, precursor is proopiomelanocortin turning into ACTH then into MSH
Secreted by anterior pituitary (or pars intermedia) and also by skin keratinocytes (involved in tanning in humans)
Functions in mammals: acquisition of brown summer hair in animals such as short-tailed weasel, suppresses appetite, increases sesual arousal, Humans: skin darkening in response to sun light (mostly via paracrine action of MSH from keratinocytes), Memory enhancement, fetal steroidogenesis, skin darkening (melanosome dispersion), Brown summer hair coat, pheromone secretion
Amphibians have melanosomes as mechanism of camouflage
Melanotan II is a synthetic analogue of the MSH. Developed for tanning, but found to support erectile function as well.
Note: besides the MSH, another pituitary hormone, the ACTH, can also stimulate melanin production. Because of this, pituitary-dependent Cushing’s disease and Addison’s disease patients, who have high levels of ACTH, exhibit hyperpigmentation
somatotropin
growth hormone, body growth
direct effect on mobilization of fuels during starvation
indirect effect on growth- IGF-1
hyper and hyposomatotropism
Follicle stimulating hormone
FSH, reproduction and gonads
luteinizing hormone
LH, reproduction and gonads
thyrotropin
TSH, thyroid stimulating hormone
adrenocorticotropic hormones
activity of thyroid and adrenal glands
besides the MSH, another pituitary hormone, the ACTH, can also stimulate melanin production. Because of this, pituitary-dependent Cushing’s disease and Addison’s disease patients, who have high levels of ACTH, exhibit hyperpigmentation
somatotropin secretion
Protein (191 amino acids) produced by somatotrophs of the anterior pituitary and also in smaller amounts by mammary glands in cats dogs and humans
Regulated by hypothalamic GHRH (somatokrinin) and GHIH (somatostatin)
secreted in pulsatile fashion during day, secretion declines with age
function of somatotropin
promotes growth and provides a ready source of energy during starvation
Traditional view: promotes growth mostly indirectly by stimulating liver to release IGF-1. It also directly stimulates carbohydrate metabolism to produce glucose. Stimulates gluconeogenesis in the liver.
baso hormone secretion
hormones have base level of secretion with peaks of secretion beyond this
tapering off of secretion of growth hormone with aging
anabolic action of somatotropin
indirect growth promoting action,
stimulates liver to secrete IGF-1. (Liver is endocrine gland)
anabolic action prevails in well-fed animals
Promotes growth via IGF-1 in liver, muscle, and bone
IGF-1
insulin like growth factor, related to insulin
stimulates lipogenesis, protein synthesis, cell multiplication, cell enlargement and also the deposition of extracellular matrix
Promotes accumulation of chondrocytes in long bone growth plates
Synthesized in almost all tissues
catabolic action of somatotropin
direct, fuel-mobilizing action, typically prevails in poorly fed animals, lipolysis
IGF-1 variation in breeds
levels correlate to size of breed. Large breeds have more IGF-1
Factors regulation growth hormone release
Many are species dependent. For example, stress increases GH in primates and decreases GH in rodents and has not impact on ungulates
Glucocorticoids have negative impact, concentration dependent
promotion by Ghrelin in stomach
Cells of mammary gland and somatotrophs of anterior pituitary produce GH so progestin (synthetic progesterone) can cause increased production of GH
Factors regulating IGF-1 release
Pituitary produces GH
Pancreas produces insulin
Intestine has good nutrition
All of these positivity feedback on IGF-1 production
Cortisol, estrogen, and malnutrition inhibit IGF-1 production
Hyposomatotropism
low level of GH
hypersomatotropism
high level of GH
Pituitary dwarfism
inherited or acquired as a consequence of prolonged administration of glucocorticoids, hyposomatotropism, failure to secrete enough of the GH in young animals
Giantism
Hypersomatotropism before epiphyseal plate closure, becomes acromegalic gigantism
acromegaly
hypersomatotropism after epiphyseal closure
Feline acromegaly is relatively rare, >8 year old male cats
Acromegaly dogs are more frequent, often associated with progestin-induced mammary hyperplasia
Diabetes melitus is possible sign as GH interferes with insulin intracellular signaling, frequently undiagnosed cause of diabetes melitus
recombinant GH
GH can be synthesized using recombinant methods
Human recombinant GH is used for the treatment of dwarfism (hormone replacement therapy). However, because of its anabolic function, it is also abused in sports.
Bovine synthetic GH (bovine somatotropin, bST) is one of top-selling cattle pharmaceutical products in US. This is because bST prevent mammary gland cell death, can be used to increase milk production. Given by injection, can’t be in feed because the protein would be broken down in digestion
Controversy: consumer groups fight bST use in milk production because of fear that bST or IGF-1 in cow milk could possibly affect human health. GH from cadavers caused spread of disease.
Unsubstantiated because: bST is not active in humans. When ingested, bST and IGF-1 are digested (not absorbed), Thus, bST treatment is considered safe by FDA. But it has been banned in Europe and Canada.
Federal law prohibits any hormone use in the poultry and pork industry
Regulation of gonadotropin
GnRH: Gonadotropin release hormone
GnRH stimulates release of Lh and FSH.
Causes germ cell development and production of estrogen, testosterone and progesterone
Gonadotropins
LH (luteinizing hormone) and FSH (follicle stimulating hormone)
Proteins (half life of a few minutes), secretion controlled by GnRH
Patterns of release: basal, pulses, surges
Positive feedback controls surges
FSH function
stimulates growth and maturation of immature ovarian follicles
Also stimulates follicular granulosa cells to produce estrogen (steroid)
LH function
triggers ovulation and development of the corpus luteum
Also stimulates follicular theca cells to produce androgens. corpus luteum (CL) produces progesterone (steroid)
Oogenesis and follicular development during estrous cycle
Females are born with ovaries that contain a finite number of primordial follicles (cow ~100,000, human ~1 million). In sexually mature females, ovaries undergo cyclic changes, Each cycle culminates with ovulation that presents the egg for fertilization
During each estrus cycle, several waves of follicles start to grow and mature. Maturing follicles secrete estrogen.
In fully primary oocyte finishes the division and becomes a secondary oocyte
primary oocyte
contained in each primordial follicle
diploid cell arrested at the stage of the first meiotic
secondary oocyte
first haploid cell division, starts the meiotic division and close to the time it is finished, it is released from follicle during ovulation
estrous cycle definition
recurring set of physiological and behavioral changes that occur in sexually mature mammalian females in a time period from one estrus to another. Controlled by pituitary and ovarian hormones.
Proestrus
build up to estrus, luteolysis is completed, follicular growth and maturation, low progesterone, high estrogen (produced by follicles), stimulates endometrial proliferation as uterus lining has regressed during anestrus,
FSH and LH stimulate follicular growth and production of estrogen. Estrogen suppresses LH and FSH secretion (negative feedback mechanism), this is mediated by GnRH
High levels of estrogen stimulates a LH surge (switch to positive feedback mechanism). The surge of LH triggers ovulation
Estrus
female becomes sexually receptive, ovulation induced
Metestrus
corpus luteum is forming, secretes Progesterone which suppresses FSH and LH secretion, stimulates endometrial secretion in preparation for implantation and also supports pregnancy
Diestrus
corpus luteum fully formed, secretes large amounts of progesterone
If not pregnant, the animal will enter proestrus after this stage, the corpus luteum regresses as a consequence of locally released uterine prostaglandin F2 alpha. The resulting decrease of progesterone levels removes LH and FSH inhibition and the cycle can start again.
If pregnant, the corpus luteum is rescued from regression by placental hormone chorionic gonadotropin in most mammals and interferon tau in cattle.
Anestrus
Activity of ovary is suppressed, could be due to pregnancy or entering season where unreceptive to breeding in seasonal breeders,
In seasonal breeders at beginning of breeding season or after parturition, animal enters proestrus. This transition is controlled by Melatonin (released by pineal gland).
Which hormone is responsible for primary follicle development?
Trick question! the development of the primary follicle is an intrinsic process in the ovary
Theca cells
means “box”, follicle is boxed in by theca cells, Ovarian cells that secrete androgens, express LH receptors, synthesize mostly androgens during follicular phase, Switch to low-level estrogen synthesis during luteal phase
Granulosa cells
ovarian cells that convert androgens into estrogen,
express FSH receptors, Synthesize estrogen during follicular phase, Produce progesterone during luteal phase, Together with progesterone, granulosa cells secrete hormone inhibin that inhibits FSH,
interaction between hypothalamus, pituitary, and ovary during estrous cycle
- GnRH travels through hypothalamo hypophyseal portal system to Gonadotropes to secrete FSH and LH
- Follicles grow in response to FSH and produce estrogen
- Negative feedback predominates from estrogen
- LH causes ovulation
- After LH surge triggers ovulation, corpus luteum produces progesterone. (stimulates endometrial secretion)
- Progesterone negative feedback inhibits further gonadotropin secretion
Gonadotropins in males
released in steady fashion to stimulate secretion of testosterone and estrogen and to support spermatogenesis.
sertoli cells
nurse cells of seminiferous tubules, receptors for FSH, analogous to granulosa cells of ovary
Leydig cells
produce testosterone, receptors for LH, analogous to theca cells in ovary
GnRH
Gonadotropin release hormone, reach gonadotrophs in anterior pituitary through portal veins
structure of ovary
vascularized medulla surrounded by cortex with follicles
spermatogenesis
with the onset of puberty, pituitary starts to produce more gonadotropins (FSH and LH). These hormones stimulate spermatogenesis. Occurs in the walls of seminiferous tubules, where germinal cells turn into primary spermatocytes which undergo meiosis, yielding 4 haploid spermatozoa. Nursed by Sertoli cells. Spermatogenesis requires high concentrations of testosterone that is secreted by Leydig cells that surround seminiferous tubules.
Immature spermatozoa are transported to epididymis where they accumulate and mature
In sexually active males, spermatogenesis is continuous and billions of sperm are produced daily.
Most of daily produced sperm is lost in urine.
Hormonal regulation of testes and testosterone function
Leydig cells of testes produce testosterone
Secretion of testosterone is regulated by the hypothalamic GnRH and pituitary LH
Pituitary FSH stimulates activity of testicular nurse cells- Sertoli cells
Testosterone
steroid hormone that stimulates spermatogenesis, activity of sexual accessory glands, development of secondary sexual characteristics, development and maintenance of libido
Chorionic gonadotropin
analogous to LH, produced by human trophoblastic cells of blastocyst, rescues corpus luteum from regression. This keeps producing progesterone, which is necessary for suppression of pituitary gonadotropins and for preventing regression of endometrium. Used for pregnancy test in humans.
Interferon tau
Produced by bovine and ovine trophoblast. Performs similar function as human chorionic gonadotropin
Placental lactogen
analog to GH and prolactin, supports maternal metabolism and initiates milk synthesis, antagonizes maternal insulin.
Relaxin
relaxes pelvic ligaments, increases oxytocin synthesis, preparation for parturition
functions of oxytocin
milk ejection, myometrial contractions during labor (together with prostaglandins), CNS effects, stimulates secretion of uterine prostaglandin 2 alpha toward the end of pregnancy, stimulates contraction of smooth muscles of reproductive organs during copulation, central release induces maternal behavior and pair bonding
Can stimulate ADH receptors, severe water retention when it is used to induce labor
alveolus
basic unit of mammary gland, hollow spherical group of milk secreting cells
milk ducts
where the alveoli empty into
lobi
groups of alveoli