Hormones and Behaviour Lecture Notes PDF

January 13th - Research Techniques in Behavioural Endocrinology Removal and Replacement: Possible to make causal interpretations -​ Removal of the source of the hormone (measurements taken before and after) Immunoassay -​ Way to detect specific biological substances in the blood and tissues...

January 13th - Research Techniques in Behavioural Endocrinology Removal and Replacement: Possible to make causal interpretations -​ Removal of the source of the hormone (measurements taken before and after) Immunoassay -​ Way to detect specific biological substances in the blood and tissues -​ Routinely used to measure hormone levels -​ Harness fundamental principles of the immune system in order to quantify or visualize specific substances -​ Immune system of one animal is hijacked to create antibodies to a substance of interest from another animal -​ Ex: Experiment looking at the effect of testosterone on mating-related aggression in male rats 1.​ Take testosterone from rat and inject it into a rabbit. 2.​ Rabbit’s body creates antibodies 3.​ Take blood from rabbit 4.​ Rabbits antibodies can be extracted and purified, and then tagged with a label so it can be detected. Radioimmunoassay -​ Type of immunoassay that uses radioactivity to detect chemical substances in body tissues -​ Pioneered by Rosalind Sussman Jalloh who won the Nobel Prize in Physiology + Medicine in 1977 -​ Requires a known radio ligand (hot ligand) 1.​ In this example, our radio ligand is hot testosterone (shown in red with asterisk). Same amount is added to 3 tubes. 2.​ Known amounts of a non radiol labeled (cold standard) is in increasing concentrations throughout the 3 tubes (shown with black T). This would be non tagged invisible testosterone, which can’t be detected like the radio ligand can. 3.​ All tubes are coated with the same amount of testosterone antibody (shown in blue) and the contents are swirled around. ​ ​ ​ ​ The hot and cold testosterone compete for the antibody ​ The excess fluid is dumped out and the amount of radioactivity stuck to the antibody in the tube is measured. ​ The more cold testosterone is added, the less hot testosterone there is binding to the antibody and therefore less radioactivity is detected. ​ By plotting the known concentrations of the cold standards on the x axis and the radioactivity on the Y axis, we can create a standard curve. ​ Cornerstone for immunoassays because it serves as a ruler for determining the amount of substance of interest in a sample. Ex: We have a blood sample from one of our experimental rats, and we want to know how much testosterone is in there. 1.​ Add our sample containing an unknown (as of yet) amount of testosterone into a tube with both hot testosterone and antibody. 2.​ Compare how much radioactivity is left after we dump out the incubation fluid 3.​ If the amount of testosterone in our unknown sample is similar to one of the standards in the standard curve, we can interpolate the amount of testosterone using the standard curve. ELISA -​ Can quantify hormones in other types of tissues like hair, nails, feces, blubber -​ Enzyme linked immunosorbent assay -​ Works on the same principles as radioimmunoassay but uses color intensity as a label instead of radioactivity. -​ Uses small quantity of samples -​ Standards of known concentrations are used to generate a standard curve -​ The darker the colour, the stronger the concentration of hormone -​ Can compare the color intensity (optical density) of unknown samples to the standard curve. Does verbal aggression alter testosterone levels in undergrads? -​ Term “alter” → tells us its an experiment 40 undergrads, randomly assigned to a neutral or insult condition. Neutral —-- Insult Saliva sample collection, elisa for testosterone -​ Via passive drool saliva collection or salivette -​ Elisa kit used for assay, multiple samples used to counterbalance human or equipment error. -​ Intra-assay variation: replicates samples within one plate (ex:multiple pipettes for S2) -​ Inter-assay variation: Running assays on various plates Briefly describe two things you need to know about a hormone in order to run an accurate ELISA ELISA applications -​ Pregnancy tests (detects HCG in urine) -​ Early ovulation tests -​ Covid tests Immunoassay Limitations -​ Hormone identity must be known -​ To create antibody -​ Antibody properties -​ Specific/sensitivity -​ Ex: an antibody that detects a hormone in mice might not be able to sufficiently detect that same hormone in birds. -​ Ex: have to be sensitive enough to the typical range of concentrations of that hormone in your tissue of interest. -​ Safety -​ ELISA safer than RIA -​ Simplicity -​ RIA: extensive permitting, long protocols -​ ELISA purchased in “kits” for quick use Quantifying Hormones Both radioimmunoassay and ELISA are used to quantify the amount of a hormone in a particular body fluid. But bodily effective amounts of hormones are quite small and difficult to measure accurately. Most hormones are measured on the order of micro or picograms. Some hypothalamic hormones are measured in femotograms - The concentration of hormones in a particular tissue is most often measured as the quantity of a hormone relative to one unit of tissue (blood plasma, urine, saliva, feces). - Quantity of hormone can be measured in : ​ - Mass: relative to the one unit (ex: nanograms/milliliter) ​ ​ - Animal research ​ - Molar: based on molar mass ​ ​ - Clinical studies, human research (picomoles/milliliter) ​ - IU: arbitrary quantity standardized to a relevant biological effect ​ ​ - Peptide hormones (insulin, thyroid hormones) bc are larger and have complex chemical interactions than other types like steroids. ​ ​ - Can be converted back to other units using a reference conversion factor found online  Figure: Tracks how four reproductive hormones change over the ovarian cycle in xx human females. *Steroid hormones estradiol and progesterone (Panel C and D) are in picomoles/liter *Peptide hormones luteinizing hormone and FSH (from pituitary gland) are in units/liter Figure: Hormone variation over the ovarian cycle in rhesus monkeys * Estradiol measured in picograms/ milliliter * Progesterone in nanograms / milliliter Mass percentage: The amount in hormone in 100 milliliters of plasma or serum -​ Done almost exclusively in clinical endocrinology research, and older animal studies -​ Can be converted to conventional approaches by standardizing to 1mL  Immunohistochemistry -​ Type of immunoassay where a labeled antibody is applied to tissue in order to visualize a particular hormone receptor or protein. -​ Called immunocytochemistry when applied to cells. Direct detection immunohistochemistry: Antibody will bind to estrogen receptors, which we can visualize and determine their location in the brain. Only requires one antibody. Indirect detection immunohistochemistry: relies on the same principles, but requires the binding of more than one antibody as well as large binding proteins like horseradish peroxidase (catalyzes chemical reactions which result in colored products that can be detected using brightfield or fluorescent microscopy). ERɑ Immunohistochemistry -​ Ventromedial hypothalamus: plays an important role in female social and sexual behaviour and has a high density of estrogen receptors. -​ Isolating mice temporarily or long term results in an increase in the density of estrogen receptors in the ventromedial hypothalamus. -​ This image was used with immunohistochemistry using an antibody targeted against the alpha estrogen receptor Autoradiography -​ Technique that reveals locations of hormone receptors by injecting a radio labeled hormone and then exposing the tissue of interest to a radioactivity sensitive film. Pharmacological technique -​ Use drugs that influence hormones and neurotransmitters by altering activity at their receptors. -​ Agonist: mimics the effects of an endogenous or naturally occurring chemical messenger like a hormone or a neurotransmitter. Most oral contraceptives are estrogen or progesterone receptor agonists. -​ Antagonist: block the effects of an endogenous chemical messenger. Ex: caffeine is antagonist at the adenosine receptor. Adenosine inhibits neuronal activity and promotes sleepiness. Brain imaging: Humans -​ noninvasive Brain imaging: Animals -​ IEG expression -​ Used as evidence for neuronal activity and detecting changes in small animals -​ Immediate early genes like ZENK (EGR-1 and NGFI-A) and C-FOS appear in neurons after they’ve been active, so immunohistochemistry can be used as an indication that neurons in a particular area have been firing. -​ Ex: Zebra finches ​ ​ ​ Suggests that this brain region plays a role in the reception of auditory signals. January 13th - Class Which technique(s) would be most appropriate to determine where hormone receptors are located in the body? (Be specific and concise) Technique How does it work Suitable for receptors (Yes/No) Immunoassay/Elisa Ligand compete for antibody no, substances in body fluids Immunohistochemistry labeled antibody is applied to Yes tissue in order to visualize a particular hormone receptor or protein. Antibody bind to a protein, can be visualized Autoradiography Reveals locations of hormone Yes receptors by injecting a radio labeled hormone and then exposing the tissue of interest to a radioactivity sensitive film. Dark spots show where the receptors are Ligand hormone is tagged, given to an animal/tissue exposed Human brain imaging structural CT scan (x-ray) No (only large structures) MRI (magnetic fields) “ function FMRI (oxygen, blood flow to FMRI, EEG → no magnetic fields) PET= hormone, but large field EEG of view PET (injection of radioactive substances) Animal brain imaging IEG IHC Immediate early genes like IEGs are not hormone receptors ZENK (EGR-1 and NGFI-A) (so no) and C-FOS appear in neurons after they’ve been active, so immunohistochemistry can be used as an indication that neurons in a particular area have been firing. Antibody for IEG, visualizes cells that have fired/have been active Week 2 - Lecture 2: Endocrine Glands Endocrine Glands -​ Ductless, release hormones into blood -​ Have wide range of action and can generally interact with any cell that has the appropriate receptor -​ Vary in chemical structure, target cells, receptors, functions and time course Parathyroid gland: Collection of four tiny rice size glands embedded within the thyroid. -​ Releases hormone called PTH -​ Raises blood calcium levels by pulling it from tissues -​ Calcium is important for functioning of the nervous system, heart, kidneys and bone -​ Not involved in behaviour. Hypothalamus + posterior pituitary -​ Responsible for the regulation and release of many hormones -​ Ex: Oxytocin -​ Has effects on a number of physiological and behavioural processes, including milk ejection from mammary glands, uterine contractions during birth, and social bonding Adrenal Gland -​ Collection of different glands -​ All use bloodstream to target tissues Types of chemical communication Intracrine communication: Chemical signalling within a cell. Chemical messenger is not released Autocrine communication: Chemical messenger is released, but acts on itself Exocrine: -​ Releases substances into ducts -​ Not released as chemical messengers -​ Once released, carried to nearby target organs or external environment -​ Salivary, sweat, mammary glands Neuroendocrine system: -​ Specialized neuron: neurosecretory cell -​ Releases its chemical messenger into blood rather than synapse -​ Its secretions are called neurohormones Adrenal medulla: -​ Releases adrenaline and noradrenaline -​ Activate fight or flight *Many other hormones are released from the adrenal cortex, but their release is not directly triggered by neuronal activity so they are not neural hormones. Noradrenaline -​ Released directly from sympathetic neurons straight into bloodstream -​ Noradrenaline acts as a neural hormone -​ Released from neuron into synapse in the brain -​ Acts as a neurotransmitter -​ Why does this matter? -​ Timecourse: neurotransmitters act much faster than neural hormones -​ So the time course of action of this chemical is dependent on where and how its released  Adrenal Gland Pancreas -​ Sis on top of each kidney and is composed of different cell -​ Endocrine and exocrine gland types arranged in layers -​ Endocrine tissue is distributed throughout the pancreas in clusters called islets of Langerhans -​ Contain 4 diff cell types: -​ Insulin is the only hormone that lowers blood sugar. No other hormone can take over this role (type 1 diabetes) Recap: -​ We can characterize hormones by their site or gland of release -​ Other ways of classifying hormones: by chemical structure or origin: 4 main types Week 2 - Lecture 3 : Peripheral hormones Thyroid Hormone synthesis 1.​ T3 and T4 are derived from the amino acid Tyrosine, specifically from a large rich protein called thyroglobulin. This can be found in the thyroid follicles 2.​ Some of the tyrosine residues attached to the thyroglobulin pick up iodine from the diet to form 2 different molecules: 3-monoiodotyrosine (MIT) and 3,5-Diiodotyrosine (DIT) -​ Lack of iodine prevents the synthesis of MIT and DIT which in turn prevents the synthesis of essential thyroid hormones that play a huge role in neurodevelopment. -​ Iodine deficiency is a preventable cause of intellectual disability and cognitive deficits. 3.​ MIT and DIT combine to form the 2 thyroid hormones T3 and T4 -​ T3 is a MIT and a DIT -​ T4 is two DITs -​ They are lipophilic (soluble in oil) -​ Can cross the fatty middle layer of cell membranes and gain access to many tissues -​ Thyroid hormone receptors are located inside the cell, like steroid hormones -​ Not soluble in blood so require carrier proteins to reach targets -​ The release of T3 and T4 is controlled by TSH, which is released from the anterior pituitary gland -​ They then affect all cells -​ Increase metabolism which results in heat production -​ In mammals, thyroid hormone levels increase in the winter -​ Influence growth by influencing the release of GH -​ Important for the development of the nervous system and can affect reproduction -​ People with hypothyroidism tend to have delayed sexual maturation and can also have reduced levels of circulating gonadal steroids. C cells -​ Embedded in the thyroid itself -​ Release calcitonin -​ Dont have an effect on behaviour Parathyroid glands -​ Release PTH -​ Dont have an effect on behaviour High levels of calcium triggers calcitonin release, which nabs excess calcium in the body and tucks it away in bones (reduces calcium in the blood). -​ PTH does the opposite. -​ When calcium levels are low, parathyroid hormone targets bone, the gut and the kidneys to increase calcium levels. *Most hormones that alter behaviour are controlled by the hypothalamus and pituitary gland. Pancreatic Hormones All cells except for the central nervous tissues have insulin receptors, and when it binds to its receptors, it is taken up into the cell and used, or stored in muscles as glycogen. Urocortin- 3: Protein that is co-released from pancreatic, alpha and beta cells along with glucagon and insulin -​ Acts on the nearby delta cells in the pancreas to release somatostatin, which acts by negative feedback to inhibit the release of insulin and glucagon. -​ Great example of paracrine communication Gastrointestinal hormones Secretin: -​ Released from the small intestine -​ Acts to increase water and bicarbonate secretion in the pancreas CCK: -​ Released in response to food entering the small intestine -​ Increases bile secretion from the gallbladder, which aids in the digestion of fats -​ Acts on brain to decrease feeding Ghrelin -​ Comes from the stomach -​ Increases gastric acid and motility -​ Acts on the brain to increase feeding -​ Stimulates the secretion of GNRH from the anterior pituitary Gastrin -​ Released by the stomach, can be triggered by neural signals sent to the stomach via the vagus nerve. -​ Can have different effects depending on its concentrations -​ Low: Acts on stomach, pancreas and liver to increase water and electrolyte secretion -​ High: Targets the pancreas to increase insulin, can also stimulate contractions of gut, gallbladder and uterus via effects on smooth muscle. Adipokine Hormones -​ Released by adipose cells Leptin: Energy expenditure hormone -​ Decreases food intake by targeting receptors in the CNS and does this by reducing the motivation to eat by acting on the hypothalamus. -​ Levels increase after we eat -​ Starvation hormone. When hungry, leptin levels fall and stimulates food intake Adrenal Hormones Gonadal Hormones 1.​ Gamete production 2.​ Hormone production Testes -​ Sperm are born and develop in seminiferous tubules -​ Sertoli cells are important in the development of sperm -​ Release inhibin -​ Regulates the release of pituitary gonadotropins by negative feedback -​ Leydig cells produce androgens -​ Wide range of effects -​ Testosterone -​ FSH -​ Gonadotropin released by the anterior pituitary -​ Not a peripheral hormone -​ Stimulates inhibin release, feedbacks at hypothalamus -​ LH -​ Pituitary gonadotropin -​ Stimulates androgen release from leydig cells Ovaries -​ Under the control of FSH and LH -​ Go through cyclical changes -​ 3 functional subunits: 1.​ Follicle: contains the egg 2.​ Corpus Luteum: Develops after the follicle ruptures 3.​ Stroma: supporting tissue -​ 2 phases -​ Follicular phase: Follicle develops to prepare for release of egg -​ Developing follicles contain granulosa cells, which produce the hormones inhibin and activin. -​ Inhibin: Suppresses hormone secretion from the hypothalamus and the pituitary -​ Activin: Enhances hormone secretion. -​ Surrounding the follicles are Thecal cells -​ Products are estrogens ex: 17 beta estradiol (E2) -​ Have widespread effects -​ LH acts on Thecal cells to produce androgens -​ FSH acts on granulosa cells and converts the androgens to estrogens via aromatase Luteal phase: Ruptured follicle turns into the corpus luteum after ovulation -​ Primary hormones produced are progestins, secreted by the corpus luteum -​ LH stimulates the corpus luteum to produce progestins -​ Cycling hormones allow for different environments. -​ Estrogen sets the stage for conception -​ Progesterone sets the stage for pregnancy Relaxin: Softens pelvic ligaments so that they can stretch to have a baby pushed through the pelvis Placenta: Endocrine gland. Placental Hormones -​ Chorionic gonadotropin (CG) -​ Maintains corpus luteum -​ Released when the blastocyst implants in the uterine wall and maintains corpus luteum. -​ Increases progesterone release, which keeps pregnancy going -​ Is detected by pregnancy tests -​ Chorionic somatomammotropin (CS), Chorionic corticotropin (CC) and Chorionic Thyrotropin (CT) -​ Mammary, adrenal and thyroid functions -​ CS important for the onset of maternal behaviours in mammals Monoamine Hormones -​ Week 3 - Lecture 1: Steroid Hormones Steroid Hormone Sources -​ Adrenal gland secretes 3 classes of steroids from its outer cortex: -​ Aldosterone (involved in potassium and sodium balance) -​ Cortisol (glucose metabolism and the stress response) -​ Androgens (can get converted into other steroids like testosterone and estrogen, important for sex characteristics and sex drive) -​ Ovaries + Testes -​ Produce gametes necessary to reproduce, but are also endocrine glands -​ Testes produce androgens (testosterone) -​ Ovaries produce androgens as well (estrogen and progesterone ) *Although androgens like testosterone are often considered male sex hormones, and estrogens/progesterones are considered female sex hormones, they are not accurate. -​ Brain -​ Produces progesterone-type hormones from glial cells -​ Not true hormones, not released into the bloodstream: act neurally Steroid Hormone Structure -​ 3 6-carbon rings, and a conjugated 5-carbon ring -​ Modification of this structure at carbon 19,20,21 converts the general molecule into different steroids. -​ Very lipophilic → can cross membranes, cannot be stored inside a cell for very long -​ Have receptors inside their target cells (intracellular), along with extracellular receptors as well -​ Require carrier proteins when travelling in the bloodstream to target tissues. Steroid Synthesis: 1st steps 1.​ All steroid hormones are synthesized from Cholesterol as a starting material 2.​ Gets converted by an enzyme into Pregnenolone (precursor for all other steroid hormones in invertebrates) a.​ Is a Pro hormone, can be a hormone itself, or be converted to another to have different effects b.​ Ex: Progesterone is also a prohormone. i.​ Released in large amounts by the corpus luteum ii.​ Levels are highest during the luteal phase of ovarian cycle iii.​ Most important role is maintaining pregnancy 3.​ Progesterone gets converted into corticoids a.​ 11-Deoxycorticosterone is the beginning of the Aldosterone pathway b.​ 17-alpha-Hydroxyprogesterone is the beginning of the Cortisol pathway *Number of Carbons on the molecule has remained stable throughout these transformations, so progestins and corticoids are called C21 steroids. They all have 21 carbons* Aldosterone -​ Increases sodium absorption and potassium excretion: mineralocorticoid -​ Responsible for ion exchange and water metabolism Corticosterone and Cortisol -​ Glucocorticoids -​ Corticosterone is the major glucocorticoid for reptiles, birds, rodents -​ Cortisol is major glucocorticoid for primates and bony fish -​ Primary function is carbohydrate metabolism Androgen Pathway (C19) -​ Removal of carbon 20 and 21 (left with 19 carbons) Testosterone (gonadal steroid) and Androstenedione (Gonadal and adrenal steroid) -​ Produced in large amounts Leydig cells in testes -​ Produced in small amounts in ovaries -​ In males: have 3 main goals -​ Spermatogenesis -​ Secondary sex characteristics -​ Muscle building DHEA (adrenal steroid) -​ Not sure what it does -​ Highest around ages 20-25 -​ Health promoting effects Estrogen Pathway (C18) 1.​ Testosterone is precursor (a carbon must be lost) 2.​ Carbon 20 is lost 3.​ Makes 19-Hydroxytestosterone 4.​ Carbon 19 is lost 5.​ Makes 17-beta-estradiol → changes ring formations, called aromatization, happens via aromatase Test Yourself: Aromatase deficiency is a rare genetic condition characterized by the absence of the enzyme aromatase. Describe what happens to steroid synthesis in individuals with this condition. Estrogen Pathway (suite): -​ In females, this process happens in the ovary 1.​ The thecal cells of the follicle produces testosterone via the androgen pathway 2.​ The testosterone travels to the granulosa cells where they get converted into estrogens Estrogens: -​ Involved in the production of the corpus luteum which produces progestins after the follicle releases the egg -​ Important in development of secondary sex characteristics, bone density and maternal behaviours Female & Male Hormones -​ Both males and females have the capacity to produce, metabolize, and respond to both estrogens and androgens -​ Ex: all male vertebrates produce progestins and estrogens, all female vertebrates produce androgens -​ Differ in the proportions/concentrations -​ Generally, ovaries have more aromatase than androgen producing enzymes than the testes -​ If there is insufficient aromatase for whatever reason, then some androgens may be secreted by the ovaries into the bloodstream -​ This can lead to abnormal endocrine behaviours -​ The same can happen to males, vice versa -​ Changes over the course of the day, seasons, or between species and individuals apply as well -​ Hormones are not a binary indicator of SEX Neurosteroids -​ Produced in the CNS and PNS from glia cells -​ Act on GABAa, NMDA and sigma receptors -​ Role is not as well characterized -​ Believed to be implicated in stress, memory, mood, affective disorders, sexual behaviours, and aggression Steroid Availability -​ Factors that influence the amount of available hormone in the blood -​ Lipophilic, so cant be stored in vesicles -​ Influenced by the rate of synthesis rather than release -​ Steroid breakdown (catabolism) influences the amount in the blood -​ Do not dissolve well in water-based blood, so depend on a carrier protein -​ The affinity of the protein carrier to the hormone also affected its ability to bring steroids to their target cells -​ Ex: if binding is really strong: Affects how readily a steroid can dissociate from the carrier protein and then enter a cell to its receptors -​ A steroid bound to a carrier protein is inactive Test yourself: the common precursor for all steroid hormones except pregnenolone is : progesterone? Week 3 - Lecture 2 : Hypothalamic and Pituitary Hormones -​ All hormones released from the hypothalamus and the pituitary gland are peptide or protein molecules. Protein and peptide molecules are synthesized from amino acids, which are translated from RNA sequences, which themselves are transcribed from DNA. Specific RNA sequences code for amino acids. Ex: TRH is 3 amino acids long, and GHRH is 44 Very similar across species Shows that the hormone hasn't changed much through evolution. Opens up opportunity for using animal models Half - life -​ Most metabolism of chemical messengers happens in the liver -​ A substance's half life is the time that it takes to get rid of half of the original amount -​ Shows that smaller peptide hormones usually have shorter half lives than longer ones Hypothalamus -​ Regulates body temp, psychological drives + behaviours -​ Ventral region of the forebrain, above the thalamus 1.​ Hypothalamic nuclei contain secretory cells (release chemical messengers into the blood) towards the pituitary gland *Not all hypothalamic nuclei have direct endocrine connections to the pituitary* -​ Ex: SCN has no neurosecretory cells, but still has a big influence on daily rhythms of hormones -​ Ex: corticosterone levels rise during the day peaking right before waking, fall at night -​ Communicates with the PVN -​ Contains secretory cells, start of the hypothalamic-pituitary-adrenal axis (HPA axis) 1.​ Kicks off hormone cascade 2.​ Releases CRH, which travels to the pituitary gland 3.​ Pituitary gland releases ACTH 4.​ Travels through bloodstream 5.​ Promotes release of cortisol (or corticosterone) from the adrenal cortex Primary HPX Axes: H: Hypothalamic P: Pituitary X: Endocrine target 1.​ HPA: Adrenal 2.​ HPG: Gonad 3.​ HPT: Thyroid Hypothalamus → Pituitary -​ Hormones are released into the median eminence -​ Travel along the infundibulum stalk -​ Into the anterior pituitary gland -​ **This is called the portal system!!** -​ 6 releasing hormones : called this because their release triggers the release of pituitary hormones -​ Thyrotropin-releasing hormone (TRH) -​ Growth hormone-releasing hormone (GHRH) -​ Gonadotropin-releasing hormone (GnRH) -​ Melanotropin-releasing hormone (MRH) -​ Corticotropin-releasing hormone (CRH) -​ Kisspeptin -​ 2 Inhibitory hormones: have effects opposite to GHRH and GnRH -​ Somatostatin -​ Gonadotropin-inhibitory hormone (GnIH) -​ Dopamine can also act as a hormone (instead of neurotransmitter) and be considered here because it inhibits the release of prolactin from the pituitary -​ Cell bodies of secretory cells that release dopamine are located in the arcuate nucleus (in hypothalamus) -​ Release into the posterior pituitary, directly from the blood -​ Vasopressin -​ Oxytocin Anterior Pituitary -​ Derived from ectoderm -​ Gonadotropins such as LH (luteinizing hormone) and FSH (Follicle-stimulating hormone) target the gonads to release gonadal steroids. Many pituitary hormones are named after the target they affect. So, the gonadotropins nourish the gonads -​ LH and FSH are stimulated by GnRH as part of the HPG axis -​ TSH is stimulated by TRH, travels to the thyroid gland to stimulate the release of T3 and T4 as part of the HPT axis -​ GH gets its orders from GHRR and somatostatin, acts on muscle, bone and other organs to promote growth. -​ Prolactin is involved in milk production, gets stimulated by TRH and inhibited by dopamine -​ ACTH is part of the HPA axis -​ MSH is a colour change hormone (discuss later) -​ Endogenous opioids, beta-endorphin and met-enkephalin are released from the anterior pituitary in humans and other mammals POMC -​ Huge polypeptide that is 285 amino acids long -​ Precursor for other hormones, considered a pro hormone -​ Can produce compounds like the endogenous opioids beta-endorphin and met-enkephalin -​ Makes ACTH -​ alpha-MSH can be found within an ACTH -​ Melano refers to its colour-changing effects in some animals Posterior Pituitary -​ Derived embryonically from ectoderm -​ Different kinds of tissue from the anterior pit. -​ Releases 2 hormones: vasopressin and oxytocin -​ Receive instructions for release directly from neurons in the hypothalamus because their axons and terminals project directly to blood vessels that pass through the posterior pituitary Vasopressin -​ Targets kidney -​ Regulates sodium absorption (results in water retention and increased blood pressure in response to blood loss) -​ Constricts blood vessels to limit blood flow and maintain fluid balance -​ Ethanol (drinking alcohol) inhibits its release, which results in the body not being able to retain water as effectively -​ This is why you pee so much while/after drinking Oxytocin -​ Although chemically similar to vasopressin, has a different function -​ Responsible for uterine contractions, social bonding and milk ejection -​ Milk ejection -​ Reflex that ensures milk is kept in storage and only released when a baby needs it 1.​ Tactile receptors on the nipple that send neural signals to the hypothalamus 2.​ Stimulates the release of oxytocin from the posterior pituitary 3.​ Travels through the blood to the mammary glands Intermediate Pituitary -​ Located between the anterior divisions of the pituitary -​ Large in amphibians and colour-changing animals -​ Adult humans don't have an intermediate lobe -​ Is present in the fetus, produces alpha-MSH and beta-Endorphin  Week 3 - Lecture 3 : Hormone Receptors 2 main categories of hormone receptors: steroid and peptide Steroid receptors -​ Fat-soluble steroids can cross membranes, so receptors are located inside target cell membrane -​ Bind directly to DNA in cell nucleus -​ In the absence of a hormone: -​ Steroid receptors are bound to heat shock proteins (HSP) -​ Molecular chaperones -​ Cannot alter DNA, just keep the receptor inactive -​ When a steroid hormone enters target cell: 1.​ Displaces heat shock protein from its receptor 2.​ Binding of a Co-activator, which enhances and facilitates transcription Cellular response of steroids is influenced by: -​ Receptors at target tissues -​ Coactivator availability Steroid Hormone Action -​ Steroid receptors are transcription factors which act to modulate the transcription of DNA -​ This means that the effects (once they bind to their receptor) are not immediate -​ It takes time to turn the instructions from DNA into RNA and then to translate this to make proteins -​ These proteins go on to exert actions on the target cell. Peptide Hormone Receptors -​ Embedded within the cell membrane rather than inside the cell -​ Have multi-unit transmembrane domain, extracellular binding domain and a cytoplasmic domain -​ Cytoplasmic domain is important in triggering cellular events of the response -​ Two main mechanisms used by peptide hormone receptors -​ Enzyme-linked mechanisms -​ G-protein coupled mechanisms Enzyme-linked peptide receptors - Use enzymes on the cytoplasmic side G-protein Coupled Receptor - Hormone itself is the 1st messenger -cAMP is the 2nd messenger -Leads to changes in the cell -Adrenergic receptors that mediate epinephrine and norepinephrine are G-protein receptors. Some activate it, some are inhibitory IP3/DAG receptor system is dependent on G-proteins upon hormone binding -​ Target enzyme is phospholipase C -​ Produces second messengers: IP3 and DAG -​ TRH receptor is an example of this, found on the cells (thryrotropes) that make TSH -​ Calcium causes the release of TSH EX: Lithium. -​ Unknown MoA -​ Recent evidence shows that its inhibition of the IP3/DAG pathway could be responsible for its therapeutic effects.