Lec 3: Introduction the the endocrine system Flashcards
Definition of hormones
hormone vs neurotransmitter
Hormonal signalling
* Hormones are Chemical messengers that travels through the blood stream targeting specific organs or tissues; (NTs need synapses to communicate, hormones don’t).
* A hormone can travel up to 2m in the blood stream (unlike hormones). We need very specific receptors for hormonal communication to make it very specific (specificity of the receptor is key to hormonal signalling).
* Coordinate the physiology and behavior of an animal by regulating, integrating, and controlling its bodily function;
* Can have more than one effect (e.g. gonadotropin hormone, and epinephrine);
* Hormonal messages can travel anywhere in the body via the circulatory system; any cell receiving blood is potentially able to receive a hormonal message.
* Hormones can have double action in different tissues. The important thing is to have receptors.
Ex: double action of the
Epinephrine Hormone
Receptors are the same but the location of where they are is different.
Forms of chemical communication
Intracrine mediation: Chemical mediation of intracellular events. Molecules produced in the body of a neuron can have a signal effect at the axonal level of the neuron.
Autocrine mediation: Autocrine cells secrete products that may feedback to affect the process in the cell that originally produced them. Ie, steroid hormones have receptors for their own secreted products
Paracrine mediation: neurons use this form of chemical communication. Chemical mediators released by one cell induces a biological response in adjacent cells.
Endocrine mediation: secrete chemicals into the bloodstream, where they may trabel to distant target cells.
Ectocrine mediation: released to the outside world/environment by an individual to communicate with other individuals. ie, pheromones.
Forms of Chemical Communication
Chemical messengers can have different names.
Cytokine = immune response
Neurotransmitter can be considered a Neurohormone (oxytocin, norepinephrine).
General features of the Endocrine System
Main features
1. Endocrine glands are ductless (closed structures - no ducts that communicate with other structures).
2. Endocrine glands have a rich blood supply.
3. Hormones, the products of endocrine glands, are secreted into the bloodstream.
4. Hormones can travel in the blood to virtually every cell in the body and can thus potentially interact with any cell that has appropriate receptors.
5. Hormone receptors are specific binding sites, embedded in the cell membrane or located elsewhere in the cell, that interact with a particular hormone or class of hormones. ie; receptors can be inside the nucleus and where they are located is important for the form of communication.
Some glands like the pancreas are both endocrine and exocrine. It secrete digestive juices into the intestines via ducts, whereas the endocrine compartment of the pancreas secretes hormones directly into the bloodstream, where they travel throughout the body to regulate energy utilization and storage.
We have another gland that communicates through exocrine communication. Rely on ducts to secrete the substance that they produce, so they produce to outside the body ie:salivary glands, mammalry gland.
More features
- Hormone receptors are either embedded in the cell membrane or located within the cell
- Receptor concentration and hormone concentration can interact – Insufficient receptors might cause endocrine deficiency (not enough receptors can be associated with resistance, ie: type 2 diabetes is a type of insulin resistance, not enough to uptake the sugar content in blood).
-
Cross-reaction - when the blood concentration of a hormone is high binding with receptors that are specific for other, other related hormones reactions can occur causing a biological response
– > they are very similar and sometimes one hormone can connect to a receptor of another hormone = cross-reaction
Chemical classes of hormones
review this
- Hormone molecules vary substantially in size and chemical properties. Some of these differences are apparent in the major classes.
- Major chemical classes of hormones: polypeptides (proteins and peptides), steroids, and amines. Some authors consider four classes (proteins/peptides, steroids, amines and lipid-based hormones)
Vary in Chemical qualities: can vary in how soluble they are, lipid-soluble vs water-soluble.
* Remember being insoluble in lipids means these hormones cannot pass through the lipid membrane.
* Water soluble (ie, polypeptides + most amine hormones):
- well diffused in plasma blood. bind to self surface
- they bind to cell surface receptors that relay information to the nucleus through intracellular signaling.
- stored and secreted by granules or vesicles (contains hormones and protein matrix). Each secretory vesicle fuses with the membrane and then the hormone diffuses into the extracellular space through exocytosis.
- They do not need transporters to pass through the membrane. They need receptors for the hormone to get into the cell.
* Lipid-soluble: (ie: steroids,testosterone):
- pass through the cell membrane easily.
- when they are produced they are secreted. They need carrier proteins when they are circulating through the blood.
- NEED TRANSPORTERS/PROTEIN CARRIERS
Chemical Classes of Hormones
- Know that some hormones need a carrier protein and are soluble in blood.
- Peptide hormones: they are released through exocytosis.
- Steroid hormones (lipid-soluble) cross the cell right away through simple diffusion. Location of receptor is typically in cell membrane or cytoplasm.
- Tyrosine hormones can have both characteristics.
- If the hormone is acting inside the nucleus, it will probably have transcriptional properties, we will activate a gene.
- Need to know: insulin, thyroid hormones, parathyroid hormones, steroid homoness (estrogen, androgen,testosterone,cortisol).
Major Human Endocrine Glands and Their Hormones
- Major endocrine glands: liver and heart are missing on this figure
- Think of it as an endocrine organ instead of endocrine gland. Some tissues like the heart or fat tissue produces hormones but is not necessarily a gland.
- Hypothalamus, central control of endocrine system
- Pituitary gland, located at the base of the skull.
- Thyroid gland, located upper throat, upper trachea
- Pancreas, close to small duodenum
- gastrointestinal tract: intestines also produces hormones (intestines are primitive structure) they have endocrine cells scattered all around.
- Adrenal glands, situated on top of the kidneys.
- Gonads, sexual reproduction
- Plancenta, female auxiliary organ that help produce hormones necessary for embryonic development. Any hormone that has chorionic in its name is produced by the placenta.
Hypothalamic hormones
- The hypothalamus comprises several collections of neuronal cell bodies, or nuclei, at the base of the brain. It receives projections from the brain.
- It has a lot of small sites that procude differenrent hormones.
Main releasing hypothalamic hormones:
- thyrotropinreleasing hormone (TRH);
- growth hormone– releasing hormone (GHRH, somatocrinin);
- gonadotropin-releasing hormone (GnRH);
- Melanotropinreleasing hormone (MRH);
- corticotropin-releasing hormone (CRH);
- and kisspeptin
We can see that they hypothalamus acts on another gland giving the signal to that gland to release the hormone. Not all hypothalamic hormones are jusr releasing hormones.
Main inhibiting hormones:
- somatostatin (inhibiting the growth hormone [GHIH]),
- gonadotropin inhibitory hormone (GnIH),
- Dopamine (DA))
Excitatory Hypothalamic hormones
Corticotropin-releasing hormone (CRH)
Synthesized within the anterior portion of the paraventricular nuclei of the hypothalamus (Pva) and it stimulates the secretion of adrenocorticotropic hormone; (just know that its in the hypothalamus) Every hormone that is releasing is acting on another gland to release hormone.
Tropin = nurishment
Gonadotropin-releasing hormone (GnRH)
Synthesized within the preoptic area of the anterior hypothalamus and it controls the release of luteinising hormone (LH) and follicle-stimulating hormone (FSH); these two hormones are fundamental in communication with the gonads. Nourish the sexual glands.
Growth hormone-releasing hormone (GH-RH)
Secreted within the ventromedial nucleus (VMN) and the arcuate nucleus (ARC) of the hypothalamus and it stimulates growth hormone (GH); Tells the glands that produce growth hprmone to release growth hormone.
Thyrotropin-releasing hormone (TRH)
Is synthesized mainly in the paraventricular (PVN) and anterior paraventricular nuclei (Pva) of the hypothalamus. The function of this hormone is to stimulate cells in the anterior pituitary gland to produce and release thyroid-stimulating hormone (TSH); involved in thyroid regulation.
Melanotropin releasing hormone (MRH)
A hexapeptide that stimulates the secretion of melanotropin; hormone that will nourish the glands that produce melatonin.
Kisspeptin
Has as an important role in initiating secretion of gonadotropin-releasing hormone (GnRH) at puberty, thus is involved in sexual maturation, but its role is not clearly described. New hormone - we dont know exactly how it works.
Inhibitory Hypothalamic hormones
Dopamine (DA)
Dopaminergic neurons are mainly located in the arcuate nucleus, and it acts as a primary prolactin-inhibitory hormone;
- dopamine has inhibitory action in the endocrine system.
- several distinct dopamine pathways
- plays a role in reward-motivation pathway, addictive behaviour in the CNS, but outside the CNS has inhibitory behavior.
Somatostatin (SOM) - inhibits growth hormone
Secreted by the periventricular region and mainly acts to inhibit the secretion of growth hormone (GH) and thyroid-stimulating hormone (TSH), though it also has inhibitory effects on insulin, glucagon and secretin production.
Pituitary hormones
- The pituitary gland was once considered the “master gland” because it mediated so many physiological processes. It is really two distinct glands fused into one.
- The two parts of the pituitary have very different embryological origins: roof of the mouth X base of the brain
- Pituitary gland and hypothalamus are close together. They have a blood portal to communicate: hypothalamus releases hormone in blood portal and pituitary gland collects those hormones.
- Pituitary gland receives a lot of commands from hypothalamus.
- Divided in 2 parts: anterior pituitary (developes from embrionic structure from the roof of the mouth), posterior part (outgrowth from the base of the brain)
Pituitary hormones: anterior
- Neurohormones from the hypothalamus reach the anterior pituitary via the portal system, a special closed blood circuit in which two beds of capillaries, one in the hypothalamus and one in the anterior pituitary, are connected by a vein. These hypothalamic factors stimulate cells in the anterior pituitary to secrete hormones into the general circulation.
- Neurons from hypothalamus released different hormones in the blood portal. This portal ensures that the blood flows in one direction from hypotahlamus to anterior pituitary.
- 2 step process: hypothalams releases hormones that tells the pituitary to release hormones.
- Growth releasing hormones released from hypothalamus and the growth producing homroens are the ones that release them.
Types of Anterior Pituitary homrones
Anterior pituitary hormones are usually considered polypeptides tropic hormones because they stimulate various physiological processes, either by acting directly on target tissues or by causing other endocrine glands to release hormones.
glycoprotein = involved in thyroid functionning and sexual development
Pituitary hormones: Posterior
Hypothalamic neurosecretory cells directly innervates the posterior pituitary. Rather than being released into a portal system, neurohormones are secreted directly into this structure, where they enter blood vessels and the general circulation more quickly.
Axonal projections are larger in the posterior pituitary and the posterior pituitary acts faster because it does not have the 2 step process. Anterior pituitary has smaller projections. Anterior axonal projections are released in the blood portal (we dont have this in the posterior).
Vasopressin and Oxytocin
Oxytocin and vasopressin made and packaged in the neurosecretory cell bodies and transported down the axons to be stored in vesicles at the axon terminals in the posterior pituitary. These act as a reservoir. They can be released in response to a neural impulse (AP) via exocytosis and enter the bloodstream. Thus, posterior pituitary hormones can be released as fast as a neural impulses!
Main function of Vasopressin
Vasopressin, also known as antidiuretic hormone (ADH) acts to retain water in the body. ADH has pressor (hypertensive) effects during serious blood loss; it causes constriction of blood vessels to help dealing with blood loss.
* It is an anti diuretic so it reductes our wish to go to the bathroom and pee.
* retain water in body
* involved in flight and fight response.
Main function of Oxytocin
Oxytocin action
➢ Influences reproductive function in mammals, important during birth, causing uterine contractions, often used medically to induce labor; Oxytocin can be used at a specific stage in birth –> induction of birth only at a specific stage of pregnancy because the oxytocin receptors are needed. It cannot be used to induce abortion.
➢ Involved in Suckling reflex: oxytocin is released into the blood in response to external stimulation of the nipple and travels through the general circulation to the mammary glands and causes milk let down. Mammary glands use ectocrine communication.
- Women that are breastfeeding may respond to the cry of a baby and start to lactate (this is like a reflex). Pairing of the cry of the baby and the suckling reflex.
Summary of Hypothalamic/Pituitary hormones
!!!watch video
black = excitatory
white = inhibitory
Pineal Gland
Pineal gland makes melatonin
❑ The Pineal gland is located at the top of the midbrain, above the third ventricle and just in front of the cerebellum;
❑ It contains secretary cells called ‘pinealocytes’ that produce melatonin (N-acetyl-5-methoxytryptamine), that resembles serotonin; Serotonin is necessary for the production of melatonin. Serotonin plays a role in depression probably why depression has effects on sleep.
❑ Melatonin is synthesized from serotonin via the amino acid tryptophan and is secreted into the cerebrospinal fluid and bloodstream, regulated by the sympathetic nervous system in response to changing light levels: as light levels fall melatonin secretion increases (melatonin secretion peaks in the middle of the night); as levels rise, secretion ceases.
❑ Thus, the pineal gland’s main function is related to the control of the circadian cycle of sleep and wakefulness by secreting melatonin.
Thyroid and parathyroid hormones
- The thyroid is a large bilateral structure found in the neck and consists of many spherical follicles, which produce thyroid hormones in direct response to thyroid-stimulating hormone released by the anterior pituitary.
- (HPT axis - hypothalamus pituitary thyroid axis). It is a 3 step process:
- hypothalamus releases the thyroid releasing hormone, the pituitary releases the thyroid stimulating hormones that communicates with the thyroid that releases the thyroid hormones (T3 and T4 have specific thyoir hormones). - The Thyroid gland produces iodinated substances dependent upon dietary levels of iodate. Low levels of dietary iodine result in reduced thyroid function and hypertrophy manifested as swellings in the neck. Iodate is very rare in nature, that is why we try and store it well in the body (able to store it for 3 months).
- The molecules of the thyroid priduce a large glycoprotein called thyroglobulin. Thyroglobulin modified is the precursor for T3 and T4.
What are the key functions of the thyroid hormones??
- The key functions of the thyroid hormones Triiodothyronine (T3), and thyroxine (T4) are:
- regulation of body metabolism;
- control of the development of the brain and nervous system;
- sexual maturation;
- temperature regulation. Regulation of thyroid varies through the seasons - Both T3 and T4 are fat-soluble, and they diffuse rapidly across cell membranes, but they need carrier protein to travel through the blood.
- The thyroid hormones act to increase oxidation rates in tissue. They have three general effects in mammals: they affect metabolism, alter growth and differentiation, and influence reproduction.
What is hyperthyroidism vs hypothyroidism?
Hyperthyroidism is an overactive thryoid. It produces too much of T3 and T4.
* hands tremure
* weightloss
* nervousness
* fast heart rate
* weaker or less frequent menstrual period (thyroid is also involved in menstrual cycle).
Hypothyroidism is an under active thyroid, does not produce enough T3 and T4.
* More common than hyperthyroidism.
* weight gain
* constipation
* fatigue
* cold sensitivity
* Ronaldo a super football player was diagnosed hypothyroidism (when it does not produce enough) and had problems with weight
Thyroid and parathyroid hormones:
Prathyroid and C-cell hormones
The hormones produced by the parathyroid gland and by the C cells of the thyroid are both protein hormones, and both are involved in calcium metabolism.
Parathyroid: It elevates blood levels of calcium (Ca2+) by increasing reabsorption of Ca2+ from the bone and absorption of Ca2+ from the gut via its effects on vitamin D3. PTH also inhibits phosphate resorption from the kidney, which reduces Ca2+ clearance.
Calcitonin (CT) is released from the C cells of the thyroid. CT acts in opposition to parathyroid hormone to lower blood levels of calcium by inhibiting the release of Ca2+ from bone.
PTH and CT are both controlled directly by blood calcium levels; there are no pituitary tropic hormones involved in their regulation. There is no releasing hormones acting on these parathyroid and calciotonin, it reacts directly to calcium.
Pancreatic hormones
The pancreas (produces insulin) functions as both an endocrine and exocrine(releasing in the body not in the blood stream) gland. Most of the pancreas consists of exocrine cells that produce and secrete digestive juices into the intestines, but nested throughout the exocrine tissue are islands of endocrine tissue called islets of Langerhans. Within these endocrine islands are four cell types:
- α-cells,
- β-cells,
- δ-cells
- polypeptide-secreting cells
δ-cells (pancreatic hormones)
δ-cells:
* Somatostatin is an inhibitory hormone released from the δ-cells of the pancreas.
* Somatostatin inhibits the release of insulin and glucagons locally (paracrine) in the pancreas. Somatostatin is also released from the hypothalamus to regulate the release of growth hormone from the anterior pituitary.
Adrenal hormones
- The adrenal glands are located atop the kidneys. Each gland consists of two distinct regions, the cortex and the medulla.
- The adrenal cortex also has distinct cellular zones with different functional roles:
- zona glomerulosa marked by whorls of epithelial cells
- zona fasciculata in which the epithelial cells are organized in orderly bands;
- zona reticularis, where epithelial cells have a disorganized appearance.
adrenal medulla
- The adrenal medulla is made up of chromaffin cells.
- During embryonic development these cells are derived from primitive neural tissue (sympathetic neurons) and after birth they function as part of the autonomic nervous system.
- The tissue of adrenal medulla receives innervations from neurons of the spinal cord- these are sympathetic nerves (involved in short term stress response) - so adrenal medulla is part of the autonomic nervous system. Important for the fight or flight response
- In response to neural signals, the adrenal medulla releases three monoamine hormones:
- Epinephrine;
- Norepinephrine;
- Dopamine;
A class of protein hormones, the enkephalins, is also released from the adrenal medulla.
Adrenal medulla hormones:
Epinephrine;
Norepinephrine;
Dopamine;
Enkephalins
- Hormones from the cortex of adrenal gland receives information through blood.
- The tissue of the medulla of the adrenal glands receives information through innervation. Efferent nerves from spinal cord that connect directly to the adrenal medulla –> involved in the short term stress response.
- Different axes of response to stress (long term and short term)
- The adrenal medulla is innvervated by the spinal cord by the sympathetic nerve fibers.
adrenal cortex
The adrenal cortex is composed of three distinct zones:
1) Zona glomerulosa: The outermost zone of the adrenal cortex. Aldosterone is released from these cells as an indirect response to low blood sodium levels. Helps you deal with low levels of sodium.
2) Zona fasciculata: The middle (and largest) zone consisting of orderly bands of epithelial cells. Glucocorticoid hormones (steroid hormones - lipid based hormones) are released from these cells in response to ACTH stimulation from the anterior pituitary.
3) Zona reticularis: The innermost zone of the adrenal
cortex, consisting of a disorganized arrangement of epithelial cells. Sex steroid hormones are often produced and released from this zone. Testes also produce these hormones.
The adrenal cortex is composed of three distinct zones:
Zona glomerulosa –> Aldosterone
Zona fasciculata. –> Glucocorticoid
Zona reticularis. –> Sex steroid hormones (testies also produce these hormones)
Gonads hormones main features
❑ The gonads have two functions, which are usually compartmentalized:
(1) the production of gametes (sperm or eggs)
(2) the production of hormones associated with sexual behaviour and sexual characteristics
- The hormones produced by the gonads, are primarily steroid hormones, and are required for gamete development and development of the secondary sex characteristics
- The functions of the gonads are regulated by tropic hormones from the anterior pituitary, known as gonadotropins.
- Gonads hormones also mediate the behaviors necessary to bring the sperm and eggs together
Gonadal Hormones
Testes main function
Testes main features
* The testes are bilateral glands, located in most mammals in an external sac called the scrotum;
* Seminiferous tubules: long, convoluted tubes in which sperm cells undergo various stages of maturation, or spermatogenesis;
Gonadal Hormones
Ovaries
Ovaries main features:
* Paired glands located in the dorsal part of the abdominal cavity, normally below the kidneys;
* Like the testes it is compartmentalized (different parts have different functions);
* Within the fetal ovary are germinal epithelia that eventually develop into primordial follicles. Infant ovaries contain about 500,000 immature, follicles. Approximately 400 eggs (ova) are ovulated by an average woman between puberty and
* menopause. –> after 400 eggs are done = no more menstrual cycle.
* Has three main functional subunits:
❑ Follicles
❑ Corpora lutea
❑ Stroma
Atresia: The continual degeneration of follicles throughout life. No additional gametes are formed postnatally
Gonadal Hormones
Ovaries
There is variation of hormones - menstrual cycle. Menstrual cycle is related to differences in the ovaries. Goes through series of steps to prepare the individual for conception.
Gonadal Hormones: Ovaries
The menstrual cycle
Steps in preparing the individual for conception:
1. Preperation of the primary follicle that contains an ovocyte (immature egg) surrounded by a layer of epthelial cells caled granulosa cells. Granulosa cells produces two peptide hormones, inhibin and activin, that regulate the hypothalamus and pituitary gland (gives feedback to hypothalamus and pituitary to release or not the gonadotropic hormones).
2. After ovum release, both the granulosa cells of the erupted follicle and the surrounding theca cells undergo rapid mitosis, and capillaries generated from the thecal cells vascularize the granulosa cells. In this way the follicle transforms into the corpus luteum
3. Corpus luteum persists for some time on the surface of the ovary and produces another class of important sex steroid hormones, progestogens.
In the follicular phase: Theca cells develops receptors for luteinizing hormone (LH) and produces androgens from cholesterol in response to LH stimulation. The granulosa cells develop FSH receptors and, in response to FSH from the anterior pituitary, convert androgens into estrogens. LH receptors are also expressed in the granulosa cells near the
time of ovulation in response to FSH and estrogenic stimulation. Stimulation of these receptors by LH causes the granulosa cells to produce progesterone
- Theca cells help the granulosa cells in producing estrogen
ovulation = ovum release
Very orchestrated cycle, will prepare uterus for implantation and the individual for conception and also prepare the uterys for implantation.
Gastrointestinal hormones - Ghrelin
Ghrelin.
* Stimulates GHRH release from the anterior pituitary.
* It is made in endocrine cells in the stomach.
* When ghrelin was administered to mice to see whether it would enhance GH secretion, their food intake and fat deposition increased.
* Human participants treated with ghrelin ate about 30% more food than individuals not given the hormone. Concentrations of ghrelin increased to peak levels prior to each meal (~80% increase) and fell dramatically after the meal
Negative vs Positive feedback
Negative feedback: A regulatory system that tends to stabilize a process when its effects are pronounced by reducing its rate or output.
- GnRH is relased from hypothalamus in response to the environmental stimuli or in response to some internal pacemaker. The GnRH stimulates release of Gonadotropins from anterior pituitary. The gonadotropins stimulate steroids and gamete production in the gonads. These resulting steroid hormones feedback to run off the GnRH in the pituitary. This shuts off the gonadotropic secretion from anterior pituitary.
Positive feedback: A regulatory process that tends to accelerate an ongoing process by increasing production in response to the end product. Generally less frequent. The positive feedback must be tighly controlled in short term situations, otherwise the equilibrium within the body would be seriously disrupted - deleterious consequences for survival.
How hormones work ?
Cellular and Molecular Mechanisms of Hormone Action
Hormonal messages, or signals, evoke intracellular responses via signal transduction: the chemical hormonal message is transformed into intracellular events that ultimately affect cell function. The sequence of events that begins with a hormone binding to its receptor and ends with the ultimate response in a target cell is called a signal transduction pathway.
* Hormones can alter gene expression by steroids going through the nucleus of the cell or if they are protein and peptide hormones that can bind to different protein and peptide hormone receptors then they can activate and intrinsic enzymatic activity. Or they can go through a two step process that uses a G protein to activate a cascade of events in the environment of the cell but not necessarily in the nucleus of the cell - doesnt have transcription activity.
Peptide Hormone Transduction that requires a second Messenger (physiological reponse to stress)
These receptors are coupled to G proteins, a class of proteins located adjacent to the intracellular part of a hormone receptor that are activated when an appropriate hormone binds tothe receptor. This part of the activated G protein activates an effector protein that converts thousands of reactants to products, thus amplifying the action within the cell
1) epinephrine is released from adrenal glands, it reaches the liver and binds to the G-protein coupled receptor (this forms the hormonal complex - receptor + molecule = hormonal complex). This hormonal complex triggers a cascade of events involving the synthesis of cAMP that acts as a second messenger.
2) cAMP, the second messenger cascade activates PKA (enzyme) that transfers phosphate groups from ATP acting as an on and off switch in many cellular functions. Activating the enzyme requires glycogen breakdwon and innactivation of an enzyme necessary for glycogen synthesis. Releases energy.
