bio 225 exam 3 umich

autocrine signaling

the target cell is also the secreting cell, cell secreting hormones to act on itself

paracrine signaling

Signal released from a cell has an effect on neighboring cells, doesn't go very far, no use of the bloodstream

endocrine signaling

Specialized cells release hormone molecules into vessels of the circulatory system, by which they travel to target cells in other parts of the body, travel very far and can impact many different cells

hormone definitions

classical: chemical substances produced by specialized organs called endocrine glands and transported through the bloodstream to other tissues where they act to elicit a specific physiological response
broad: chemical substances released by one cell which act on another cell
-they transmit messaged throughout the body to most if not all tissues

exocrine glands

external environment, have ducts, poorly vascularized
ex: eccrine, lacrimal, salivary, mammary, sebaceous, mucosal, prostate

endocrine glands

internal environment, usually to blood stream, no ducts, highly vascularized
ex: hypothalamus, pituitary, pineal, thyroid, adrenal, testes/ovaries

cushings syndrome

too much cortisol, usually caused by tumor in pituitary gland, prolonged exposure to glucocorticoids, high BP, round "moon" face, abdominal obesity, thin extremities, thin skin and stretch marks, fat pad between shoulder blades, hirsutism , classified as ACTH dependent (more common) or independent

addisons disease

not enough cortisol, primal adrenal insufficiency, inadequacy of cortisol and aldosterone, produced by adrenal glands, darkening of skin in certain areas, low BP, vomiting, lower back pain, anxiety and depression, fatigue and muscle weakness
what JFK had! mostly autoimmune disease, generally occurs later in life, associated with high plasma [ACTH] loss of negative feedback

graves disease

hyper (overactive) thyroids, opthalmopathy, insomnia, hand tremors, hyperactivity, hyperhidrosis, excessive sweating

classes of hormones

1. peptides
2. steroids
3. amines
4. lipids
5. purines
6. gases
-structure of the messenger affects the signaling mechanism (hydrophobic v hydrophilic)

peptide hormones

hydrophilic, soluble in aqueous solutions, travel to target cell dissolved in extracellular fluid, bind to transmembrane receptors (signal transduction), rapid effects on target cell
-produced as preprohormones, pre sequence targets polypeptide for secretion to the Golgi bodies, where the pro is cleaved off activating the hormone

AVP

ADH, works to control BP by increasing water reabsorption (increasing cell permeability to water) and constricts arterioles which increases BP, AVP has extra sequences to allow it to be folded correctly that are eventually cleaved off
1. binds to GPCR
2. receptor activates adenylate cyclase, increasing cAMP and activating PKA
3. phosphorylation of cytoskeletal and vesicle proteins ovvurs
4. triggers translocation of vesicle to cell membrane with insertion of aquaporins

amine hormones

posses -NH2, ie acetylcholine, catecholamines, serotonin, melatonin, histamine, thyroid hormones, sometimes called biogenic amines, some "true" endocrine hormones, some neurotransmitters, some both, most hydrophilic, except thyroid which are hydrophobic, diverse effects

steroid hormones

derived from cholesterol, synthesized by smooth ER or mitochondria, three classes mineralocorticoids, glucocorticoids, reproductive hormones, hydrophobic so can diffuse through plasma membrane, cannot be stored in cell so synthesized on demand, transported to target cell by carrier proteins, can bind to intracellular or transmembrane receptors, slow effects on target gene (gene transcription), cortisol has rapid non-genomic effects

mineralocorticoids

steroid hormone, electrolyte balance

glucocorticoids

steroid hormone, stress hormones (cortisol)

reproductive hormones

steroid hormone, regulate sex-specific characteristics

receptors

on target cells, hydrophilic messengers bind to transmembrane receptors, hydrophobic bond to intracellular receptors, receptors change shape or confirmation when bound by the ligand, three domains: ligand binding domain, transmembrane domain, and intracellular or functional domain

ligand

chemical that binds to the recepor, agonist (activate) or antagonist (deactivate, prevent ligand binding)

ligand receptor binding

L + R --> L-R
formation of complex causes response, more free ligand or receptors will increase the response, receptors can become saturated at high levels at which point response is maximal

law of mass action

the rate of a chemical reaction is proportionate to number of ligands and receptors but receptors can become saturated at high levels at which point response is maximal, can also be affected by affinity of ligand for receptor (low affinity takes longer to reach saturation even with same #s)

inactivation of LR complex

1. ligand is removed into circulatory system and degraded in liver or kidney
2. ligand can bind to a receptor and then get removed by an adjacent cell or degraded
3. sometimes specific digestive enzymes will degrade the ligand
4. the ligand receptor complex can be endocytose and degraded by the lysosomes within the target cell (most common)
5. the receptor can be inactivated through phosphorylation to modify the receptor
6. some cells can inactivate the transduction pathway, so the message is received but the receptor can't signal transduct

LR interactions

-a ligand may bind to more than one type of receptor: receptor isoforms, expressed on different target cells that have different responses to the same ligand
-a single cell may have receptors for many different ligands
-receptors may be promiscuous, accept many different but related ligands

intracellular receptors

usually hydrophobic, ligand diffuses across membrane, binds to receptor in cytoplasm or nucleus and changes its confirmation, LR complex binds to specific DNA sequences and regulates the transcription of target genes (increases/decreases production of specific mRNA)

types of receptors

ligand gated ion channels, receptor enzymes, GPCRs, intracellular receptors

guanylate cyclase

membrane receptor with enzymatic activity
1. ligand binds to receptor guanylate cyclase, changing its confirmation
2. activated receptor catalyzes GTP to cGMP
3. cGMP acts as secondary messengers, binds to PKG
4. PKG phosphorylates serine and threonine residues

tyrosine kinase

1. ligand binds to receptor
2. receptor dimerizes and autophosphorylates
3. phosphorylated receptors interact with protein kinases
4. protein kinases signal to Ras protein
5. Ras switches between active (bound to GTP) and inactive (bound to GDP)
-guanine nucleotide releasing proteins increase Ras activity
-Ras activation starts the MAP kinase cascade
MAPKKK to MAPKK to MAPK which phosphorylates many other protein kinases, transcription factors, and other cellular proteins (amplification!!!)

serine threonine receptor

directly activate phosphorylation cascades
1. ligand binds to type 1 TGF-B receptor
2. bound receptor dimerizes with type 2 recepor
3. type 2 receptor phosphorylates type 1 receptor, activating it
4. activating receptor phosphorylates a SMAD protein
5. activated SMADs enter the nucleus and regulate gene expression

GPCRs

1. ligand binds to a Ga protein coupled receptor, causing a conformation change
2. the as subunit releases GDP, binds GTP, moves through the membrane, and activates adenylate cyclase
3. activated adenylate cyclase catalyzes the conversion of ATP to cAMP
4. cAMP binds to PKA, which dissociates from the catalytic subunit, activating it
5. activated catalytic subunit phosphorylates proteins, causing a response
6. phosphorylated proteins are rapidly dephosphorylated by serine/threonine residues, terminating the response
7. when ligand binds to a Gi protein coupled receptor the ai subunit inhibits adenylate cyclase, inhibiting the signal transduction pathway

hypothalamus-pituitary axis

hypothalamus synthesizes and secretes neurohormones --> hypothalamic-pituitary portal system --> anterior pituitary releases hormones
-hypothalamus is directly connected to posterior pituitary, and indirectly connected to anterior pituitary
-anterior is composed of epithelial cells and produces several peptide hormones
-hypothalmaus sends neuron messengers which release neurohormones into the blood that travel to the AP, these neurohormones travel to the pituitary where they exit the blood stream to target the endocrine cells in the AP ~~~ aka the portal vein system

anterior pituitary

anterior pituitary releases hormones after stimulation from the HT

tropic hormones

hormones that stimulate other glands to release their hormones (can be second order, third order)

growth hormone

hormone secreted by anterior pituitary gland that stimulates growth of bones
-gigantism: increased early in life
-acromegaly: increased later in life
-deficient: short stature or dwarfism
-receptor insensitivity: dwarfism
-HT releases GHRH and GHIH, either stimulate or block PP from releasing GH, GH either goes to liver or somatic tissue where it causes somatic growth

prolactin

synthesized by posterior pituitary and action is on the human mammary gland, named for its actions on lactation, stimulates milk synthesis, also plays important role in maternal behavior through effects on the brain, and is found in all vertebrates
-other actions
1. osmoregulation: most primitive, can be involved in embryonic osmoregulation
2. reproduction: more concerned with consequences of reproduction
3. development: mostly amphibians, considered to be tadpole GH
4. metabolism: of lipids and glycogen
5. integument: skin, affects on hair growth, sebaceous glands, feathers in birds, pigmentation
6. behavior effects: maternal behavior

thyroid stimulating hormone (TSH)

control the secretion of thyroxine by the thyroid gland, thyroxine involved in digestion, heart and muscle function, brain development, maintenance of bones, cretinism is caused by insufficient thyroid hormone during fetal and neonatal development, condition of severe mental retardation and growth defects
-also involved in metabolic/thermogenic roles, cold sensed --> hypothalamus releases TRH --> triggers release of TSH from pituitary --> travels to thyroid and triggers release of T3 and T4 --> increases metabolism and increases body temperature
-negative feedback loop, if T3/T4 too high, inhibit TSH from pituitary and TRH from hypothalamus

adrenocorticotropic hormone (ACTH)

regulates secretion of corticosteroids by the adrenal cortex, is part of the stress response system
-CRH release by HT, enters pituitary, induces release of ACTH, which travels to adrenal gland to release cortisol, which travels to other organs to cause many responses
*due to stress

posterior pituitary

extension of the hypothalamus, has its own blood vessel system (not portal vein system), neurons originate in HT and terminate in posterior pituitary, two important hormones: oxytocin and vasopressin, stored in vesicles in axon for release via exocytosis, first order feed back loops, HT produces AVP and OT and they are stored in PP for release

pancreatic exocrine gland

produces pancreatic enzymes and sodium bicarbonate which are both excreted by the pancreatic duct

pancreatic endocrine gland

produces insulin and glucagon which are necessary for glucose regulation

insulin

from pancreatic beta cells, lowers blood glucose under hyperglycemia, anabolic, regulates metabolism of carbs, fats, and proteins, promotes the absorption of glucose from blood, promotes glycogenesis and lipogenesis, triggered by high blood glucose, synthesized as proinsulin with 3 chains, folded into golgi and one chain chopped off, its important for correct folding of insulin

glucagon

from pancreatic alpha cells, raises blood glucose levels under hypoglycemia, catabolic, regulates metabolism of carbohydrates, promotes glycogenolysis, lipolysis, gluconeogenesis, triggered by low blood glucose

somatostatin

delta cells, inhibitory hormone, inhibits GH, TSH, adenyl cyclase, prolactin, release of insulin and glucagon, surpasses the exocrine secretions of the pancreas

gastrin

triggers stomach cells to produce HCl

VIP

vasoactive intestinal peptide, stimulates the intestine to release water and salts back into the intestinal tract

additivity

when two hormones work in the same way on the same target and they do 1+1=2

synergism

when 2 or more hormones work together to increase the target cell response much more than expected by additivity (1+1>>2)

type 1 diabetes mellitus

endocrine defect, loss of beta cells of the pancreas, little or no insulin being produced
-causes: autoimmunity (genetic?), any trauma or substances that could cause a detriment to the cells of the pancreas (radiation for pancreatic cancer, surgical removal of part of all of pancreas, toxins that cause damage to islets), some idiopathic
*consequences
-essentially whole body effected
-hyperglycemic: heavy breathing, low pH, usually results from not taking insulin
-hypoglycemia: normal breathing hypothermia present, too much insulin taken
-chronic vascular diseases
-affects heart, lungs, eyes, skin, veins
-treatment: strict control of diet/metabolism, insulin replacement therapy, some new insulin agonists (trulicity), dietary control,
no cure or prevention method available

type 2 diabetes

non insulin dependent diabetes mellitus, accounts for 80-90% of all cases of diabetes in the US, most patients generally have some level of obesity, caused by insulin resistance, may have normal or higher levels of insulin released by pancreas, deficiency in response of pancreatic beta cells to glucose, patients are insensitive to endogenous insulin, correlates with excess abdominal fat, abnormally high waist to hip ratio, excessive abdominal fat, inflated fat cells and over-nourished liver/muscle cells, resist deposit of glycogen, so it stays in the blood, hyperplasia (proliferation) of pancreatic beta cells, normal/increased insulin in mild forms of T2D, difficult to treat because not just one cause: reduction in insulin receptors, mutation in insulin receptor gene, could be due to signal transduction pathway
-complications: heart disease, stroke, kidney disease, eye problems, possible blindness, diabetic neuropathy and nerve damage, in feet specifically, depression
-treatment: lifestyle changes, more exercise, less sweets, controlled diet

vertebrate stress response

hypothalamus-pituitary-adrenal axis
-HT: secretes corticotropin releasing hormone (CRH)
-AP: secretes ACTH
-adrenal cortex secretes cortisol, stimulates target cells to increase blood glucose level
-chronic stress can lead to inflammatory diseases
-interaction between nervous and endocrine systems
-sense organs detect stress, activation of sympathetic nerves, increased HR, respiration, dilation of airways, decreased secretion of insulin from pancreas, increased secretion of glucagon from pancreas, increased secretion of epinephrine from adrenal gland, increase in blood glucose level

adrenal gland

two parts
-medulla: (amines), has chromaffin cells, produces catecholamines, epinephrine, norepinephrine, dopamine as an intermediate
-cortex: (steroids), has interrenal cells, corticosteroids, glucocorticoids (cortisol), mineralocorticoids (aldosterone), androgens

effects of glucocorticoids

proteins and fats broken down and converted to glucose, leading to increased blood glucose; partial suppression of immune system

effects of mineralocorticoids

retention of sodium ions and water by kidneys, increased blood volume and blood pressure

isoreceptor

multiple receptors on multiple targets producing multiple results from the same ligand
-epinephrine can bind to receptors on liver, skeletal blood vessels, intestinal blood vessels, all different types of GPCRs

asexual reproduction

progeny are genetically identical or very similar to their parents ex: budding, fragmentation, pathernogenesis

budding

a type of asexual reproduction, an outgrowth of the parent splits off and becomes a fully formed adult

fragmentation

type of asexual reproduction, a portion of the parent breaks off and grows into a fully formed adult (like starfish)

pathenogenesis

asexual reproduction in which an egg develops without fertilization (could be haploid or diploid) ex: whiptailed lizard, two females simulate copulation with induces oogenesis

sexual reproduction

reproduction of progeny from two parents that contribute nearly equal amounts of genetic material, usually haploid + haploid = diploid

sexual reproduction advantages

creates genetic variation at 3 levels: haploid gametes from diploid parents (spermatogenesis and oogenesis), recombination creates hybrid chromosomes, diploid off spring produce unique genetic combinations, creams population of distinct genotypes

hermaphrodites

capacity to produce egg and sperm
-simultaneous: produce egg and sperm at the same time
-serial: change sex in response to environmental cues
-protogynous: females --> males
-protoandrous: males --> females

sexual reproduction cycle

1. starts as sperm and ovum (fertilization)
2. combines to form zygote (2 cell stage)
3. zygote begins to divide and differentiate into blastula (empty ball of cells)
4. more differentiation into blastula
5. gastrulation: different layers (endoderm, mesoderm, ectoderm), eventually become diff organs
6. morphogenesis when gastrula develops into what looks more like the adult animal
7. some animals under metamorphosis
8. juvenile animal: fully formed but not sexually developed
9. adult animal: fully formed and sexually developed
10. post reproductive adult
11. senescence (aging) and death

sex determination

-mammals: determined by Y chromosome, males XY and females XX
-birds and butterflies: heterogametic female (ZW), homogametic male (ZZ)
-honeybee (and some ants): fertilized: diploid female, unfertilized: haploid male

sex determination by environment

temperature dependent sex determination (TSD), common in reptiles, temperature of egg incubation determines sex, may be due to hormone levels in egg
-early spring: more males, later in season (warmer): more females, same with inside and outside of nest

gametogenesis

process by which gametes are produced, start with 2n and replicated DNA, then split to 1n replicated DNA, then split into 1n unreplicated DNA
-in males 4 sperm are made but they still have to mature, in females only 1 mature egg and 3 polar bodies

ovipary

ova laid and all development occurs externally, fertilization can be internal or external, fish, reptiles, birds

vivipary

young develop within the female body, fertilization is internal, mammals and a few other taxa

ovovivipary

ova "laid" within the mothers body, develops and hatches internally until birth, some reptiles and fish

GnRH

gonadotropin releasing hormone, synthesized and released from HT, delivered to AP, regulates FSH and LH release

gonadotropins

peptide hormones from the AP, control steroid hormone synthesis in vertebrates, include FSH, LH, hCG, only in primates, synthesized by the placenta

reproductive steroid hormones

derived from cholesterol, regulation via gene expression, bind to a nuclear hormone receptor in target, in vertebrates they are produced in the gonads, androgens and estrogens

leydig cells

adjacent to seminiferous tubules in the testicle, produces testosterone in the presence of LH

sertoli cells

part of the seminiferous tubule helps the process of spermatogenesis and the production of sperm, activated by FSH, also can produce inhibin which works in a negative feedback loop to down regulate FSH

epididymis

6-7 m long in humans, single, very narrow tube, as sperm enter they begin maturation and near completion by time they exit, secretes intraluminal solution in the environment which suppresses sperm motility until ejaculation

vas deferens

tube that carries sperm from the epididymis to the urethra, passes through prostate and bulbourethral gland

urethra

in penis and is tube for conductance of both urine from the bladder and semen from the testis

seminal vesicles

produce 70-85% of seminal fluids

prostaglandins

support sperm and also soften mucous of cervix and cause reverse contractions on the female reproductive tract to ensure sperm are not expelled

prostate glands

secretes more fluid which becomes the semen

bulbourethral glands

release a pre-ejaculate which acts as a lubricant and acid neutralizer to prepare for ejaculation

spermatogenesis

-in most species, males produce sperms continuously though life
-tested produce spermatozoa in the seminiferous tubules
-leydig cells: produce testosterone
-spermatogenic cells: sperm at different stages in their life cycle
-sertoli cells: fill gaps between cells and aid in development
-spermatids become sperm, lose cytoplasm and develop axoneme at base of flagellum, condense DNA into nucleus
-nearly mature spermatozoa that cannot swim released into the lumen of the tubule
-sperm stored in epididymis to mature further and develop swimming ability

sperm release

-during ejaculation, sperm propelled by cilia or smooth contractions along the vas deferens which connects to the urethra
-seminal fluid added by exocrine glands (seminal vesicles, prostate, bulbourethral)
-in some species sperm are only capable of fertilizing an egg after entering the female reproductive tract (mammals)

external fertilization

most common in aquatic animals, huge numbers of gametes are released, egg release and sperm release are synchronized, more cells = more chance for successful fertilization

internal fertilization

most common in terrestrial animals, avoid gamete desiccation, provide protection for embryos, usually associated with mating behavior and accessory sex organs
-copulation: permits sperm to move directly from male reproductive system to female

mammalian penis

changes in blood distribution change the penis shape (erection), due to increased blood inflow and reduced venous return causes engorgement, initiated by nerve signals from the CNS, some mammals also have a bone or cartilage within the penis

CNS control of erection

1. nerves from brain send signal to vascular smooth muscle in the penis
2. nitric oxide produced by the nerves activates a soluble guanylate cyclase
3. guanylate cyclase activity increases with the concentration of cGMP
4. elevated cGMP stimulated PKG
5. PKG phosphorylates myosin light chain kinase, stimulating it
6. PKG phosphorylates myosin light chain kinases, inhibiting it
7. PKG also phosphorylates Ca channels, inhibiting them to reduce Ca levels
8. these changes cause vascular smooth muscle to relax, allowing the changes in blood flow that induce an erection

sperm activity

various chemical signals affect this, chemokinetic molecules stimulate sperm to swim faster, chemotaxic molecules induce sperm to swim toward its target, types of chemicals include amino acids, peptides, sulfonated steroids, chemicals may be released by female reproductive tract or by the ovum

sperm storage

some females have specialized compartments for sperm storage, ova fertilized long after mating, some species retain sperm for years before fertilization takes place, allows for reproduction even when males are encountered infrequently

ova production

-ovary composed of ova producing oogonia and surrounding somatic cells
-oogenesis progresses to primary oocyte stage early in female's life, but final steps delayed until later
-follicle cells orchestrate oogenesis via paracrine factors and cell to cell contacts
-prior to ovulation, some follicles stimulated to mature (folliculogenesis)(others reabsorbed)
-vertebrate oocytes grow by accepting material from somatic follicle cells
-when follicle ruptures, the ovum escapes the ovary and moves into the coelom
-in most animals, the ovum enters an oviduct that carries the ovum to the uterus

follicles

in ovaries, contain the maturing ova

corpus luteum

in ovaries, a mass of cells that form and produces progesterone during pregnancy, also produces some estrogen, which inhibits further release of GnRH from the HT, a new one develops each menstrual cycle

ovaries

a pair, connected to the uterus and vagina by the oviduct, site of ova development and ovulation, storage of immature ova

fallopian tubes

aka oviducts, horn shaped branches of the uterus leading to the ovary, usual site of fertilization, fertilized egg will travel down the fallopian tubes to the walls of the uterus where it will implant and grow

uterus

is composed of 2 layers called endometrium and mesometrium collectively known as the uterine wall, where the ova ends up implanting if fertilized

cervix

opening to the uterus through the opening to the external anatomy, contains many glands which produce mucins and water, consistency of this changed throughout a women's fertility cycle, can aid/prevent fertilization, when pregnant, makes a mucosal plug which protects uterus from germs!

estrous cycle

-sexual receptivity coincides with specific phase of cycle
-amount of uterine tissue lost is minimal to moderate
-present in most mammals except some primates
-when fertile females exhibit behavioral cues and pheromones, called "estrus" or "heat"
-usally females only receptive to copulation during heat

menstrual cycle

-sexual receptivity occurs at many phases of the cycle
-amount of uterine tissue lost is substantial
-present only in some primates with a few other exceptions
-has 3 phases, follicular phase, ovulation, and luteal phase

follicular phase

-in each ovary, we have a number of follicles, in each follicle is one primary oocyte, surrounded by 2 layers of cells
-at very beginning, up to 25 follicles will begin to grow, but only one will become very large and rupture, called the dominant follicle
-anterior pituitary releases FSH and LH
-FSH stimulates growth of follicle --> progesterone, granulose cells produce estrogen in response to FSH
-LH makes the thecae cells produce androstenedione --> estrogen
-as estrogen and progesterone rise they inhibit FSH and LH because the follicle is already developed
-inhibin also produced by granulosa cells
-huge rise in LH and FSH toward end of follicular phase, levels fo estrogen and progesterone so high that it becomes positive feedback, causing LH and FSH to rise, thus stimulating follicle to rupture and ovulation to occur

ovulation

ovum is released by the follicle and out of the ovary to the fallopian tubes for fertilization, can either be fertilized which leads to implantation, or no fertilization in which case the cycle starts over, remainder of unused follicle becomes corpus luteum

luteal phase

left over ruptured follicle begins to change into corpus luteum, which lasts for around two weeks if no fertilization
-FSH and LH both drop because not needed, FSH drops more because of inhibin A, which is produced by the corpus luteum
-inhibin retains the CL through LH being higher and FSH being lower
-CL mass produces progesterone and some estrogen
-in no fertilization, CL doesn't have the levels of FSH and LH to maintain it so it dies :( this causes estrogen and progesterone levels to drop, when they drop enough, the endometrium can't be maintained, contractions can't be dampened, and menstruation happens and then the cycle starts over!
-in case of fertilization, blastocyst (embryo) becomes implanted into endometrium, produces hCG which keeps the CL alive, when placenta is large enough it takes over progesterone production from the CL

progesterone

maintains uterine lining in preparation for gestation, preparing the endometrium for fertilized egg implantation, does this by stimulating the development of special blood cells which provide nutrients and good blood flow, also stimulates uterine secretions which are good for embryo development, also dampens smooth muscle contractions in uterus (cramps during ur period), this was CL controls the uterine lining prepping it for growing an embryo in case of fertilization