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method of hormone release

pulsatile: especially important in hypothalamus and pituitary

biologically active concentration of hormone

very small; generally nano- to picomolar amounts

characteristics of hormone receptors

high affinity and high specificity

ablation

removal or whole or portion of gland to study the function of the gland

replacement therapy

method of studying gland following ablation; hormones are given to determine the physiological effect of the absence of the gland.

regulation of hormone secretion

a product of hormone action in target cells regulates secretion by a direct mechanism operating in the glandular cells themselves

hypothalamic-hypophyseal system

important in regulation of glandular secretion; location of important feedback mechanism

endocrine

glandular cells secrete hormone directly to blood

neuroendocrine

neuron secretes hormone directly to blood

paracrine

glandular cells secrete hormones into the lumen

neurocrine

secretion of neurotransmitters into synapse

autocrine

secreted hormone acts on releasing cell

Polypeptide hormone biosynthesis and action regulation

transcription, posttranscriptional processing of precursor mRNA, mRNA stability, mRNA export from nucleus to cytoplasm, mRNA translation, Posttranslational processing, polypeptide folding and subunit assembly, degradation, secretion

covalent posttranslational modifications of polypeptide hormones

glycosylation, iodination, sulfation, amidation, acetylation, phosphorylation

insulin

produced by Beta cells in the islets of Langerhans in the pancreas; release stimulated by increase in blood glucose levels

glucagon

produced by alpha cells in the islets of Langerhans in the pancreas; release stimulated by decrease in blood glucose levels

adenohypophysis

anterior pituitary; not innervated!

rathke's pouch

fetal structure; invagination of the oral ectoderm that leads to development of the anterior pituitary

sella turcica

depression in the sphenoid bone that houses the pituitary

pituitary portal system

vascularization of the pituitary; resulting in transfer of hypothalamic secretions to anterior pituitary for regulation

pars distalis

location of most anterior pituitary hormone production

basophil hormones

glycoprotein hormones which are comprised of two chains: alpha subunit is conserved throughout a species, beta subunit confers specificity. Examples include LH, FSH, TSH, ACTH

Luteinizing hormone (LH)

stimulates formation of the corpus luteum and ovulation in female; stimulates testosterone secretion in males

Follicle Stimulating Hormone (FSH)

Stimulates follicular selection and development; upregulates LH receptors; stimulates androgen binding protein (ABP) by Sertoli cells in males

Thyroid Stimulating Hormone (TSH)

stimulates thyroid hormone production T4 and T3

acidophil hormones

protein hormones which show great conservation of structure. Examples include prolactin and growth hormone

prolactin

stimulated mammary development and lactogenesis in female mammals, crop sac and brood patch development in birds, necessary for corpus luteum maintenance in rodents; frequently acts in permissive manner with estrogen, progesterone, glucocorticoids, insulin and growth hormone

Growth Hormone (GH)

responsible for stimulating growth; stimulates gluconeogenesis and is protein anabolic. Effects are mediated both directly and indirectly through somatomedins produced in response to GH. Release is increased by hypoglycemia and sleep

Adrenocorticotropic hormone (ACTH)

protein hormone that acts on andrenal cortex to stimulate steroid production (mainly glucocorticoids, but also some mineralocorticoids)

POMC

important steriod precursor molecule; BIG! found in posterior, intermediate and anterior pituitary. released early in the morning. precursor to ACTH and endorphins

MSH

controls melanin pigmentation in most vertebrates

beta-lipotropin

stimulates lipolysis in adipose

endorphins

endogenous opiate-like molecules

pars intermedia

area between anterior and posterior pituitary

significance of the neuroendocrine system

enables hypothalamus to act as a neuroendocrine transducer; passes information from CNS to other somatic cells

Gonadotropin releasing hormone (GnRH)

decapeptide hormone stimulates release of LH, FSH. Release is pulsatile

Thyrotropic releasing hormone (TRH)

tripeptide hormone stimulates release of TSH

Somatotropic Releasing Hormone (SRH)

44 amino acid peptide stimulates release of GH, inhibited by inhibitor hormones, brain and pancreas effects and stress

Prolactin Releasing Factor (PRF)

stimulates release of prolactin

Oxytocin

hormone that stimulates prolactin release, milk letdown in mammary gland, contraction of uterus

Prolactin inhibiting factor (PIF)

inhibits prolactin release; DOPAMINE

Corticotropin releasing hormone (CRH)

41 aa peptide hormone stimulates ACTH release

MIF

MSH release inhibiting factor

neurosecretory neuron

synthesizes and secretes a releasing hormone to be passes to primary plexus (component of the hypothalamus)

hypophysiotropic area

hypothalamus; nourishes pituitary

pars nervosa

posterior pituitary

paraventricular nuclei

structurally and functionally unique nuclei responsible for secretion of hypothalamic hormones

Prolactin regulation

performed by dopamine release (inhibitory)

Neuroendocrine integration of LH release in females

GnRH released in high pulse manner

Neuroendocrine integration of FSH release in females

GnRH released in slow pulse manner

GnRH1

conserved in all mammals; differs in one amino acid in birds

GnRH2

highly conserved in all species; involved more in behavioral processes than in gonadotropin release

effect of estrogen secretion on ovary

upregulation of GnRH receptors

Neuroendocrine integration of LH and FSH release in males

GnRH regulates pituitary release of LH and FSH as dictated by testosterone feedback

GnIH

12 amino acid peptide hormone released to median eminence of pituitary from hypothalamus; increases during non-breeding season

location of melatonin production

pineal gland and brain in mammals

neuroendocrine integration of TSH release

Stimulation from limbic structures and preoptic area stimultes hypothalamus which releases TRH into portal system and stimulates TSH release from pars distalis; T3 and T4 feedback to hypothalamus to dictate further release

neuroendocrine integration of GH release

GHRH and somatostatin released together to regulate GH release; IGF1 feeds back to hypothalamus

Ghrelin

produced by the stomach when hungry

Neuroendocrine regulation of ACTH release

CRH and vasopressin act on anterior pituitary to dictate release; glucocorticoids feedback on hypothalamus

neurohemal organ

posterior pituitary; storage area where products of neurons are released to the bloodstream

posterior pituitary hormones

oxytocin and vasopressin (ADH)

magnocellular neurons of hypothalamus

paraventricular nuclei; supraoptic nuclei; synthesize posterior pituitary hormones

site of oxytocin synthesis

paraventricular nuclei of hypothalamus

site of vasopressin synthesis

supraoptic nuclei of hypothalamus

Neurohypophysin 1

oxytocin associated; estrogen stimulated

Neurohypophysin 2

vasopressin associated; nicotine stimulated

stimulus for secretion of posterior pituitary hormones

action potential

vasopressin

regulates extracellular fluid volume; promotes water movement

oxytocin mechanism of action

phospholipase c

vasopressin mechanism of action

receptor linked to adenylate cyclase system; stimulates water retention, works on ascending loop of henle

oxytocin release stimulation

vaginal or nipple stimulation; hemorrhage, stress, estrogen

oxytocin release inhibition

severe pain, increased temperature, loud noise

vasopressin release stimulation

water deprivation, hemorrhage, pain, stress, increased temperature, opiates, nicotine, prostaglandins,angiotensin II

vasopressin release inhibition

decrease in temperature, ethanol, cardiac hormones

neurophysin

associated protein secreted in equimolar amounts with pituitary hormones

V1 receptors

modulate vasoconstriction

V2 receptors

mediate vasopressin at cellular level in kidney

classical endocrine experiment

remove gland, see what happens, give replacement therapy

compensatory hypertrophy

remaining gland gets bigger

bioassay requirements

need not be conspecific

physiological dose

dose of hormone placed experimentally in blood equivalent to that observed in an intact animal

pharmacological dose

unusually high dose of hormone placed experimentally in blood

parabiosis

attachment of the circulatory system of one animal to another animal; used to determine the presence of an endocrine factor

radioimmunoassay principle

set up competitive binding for antibody binding sites between labeled and unlabeled hormones

RIA assumptions

equal binding affinity for labeled and unlabeled hormones

RIA requirements

antibody (steroid or protein hormones); steriod hormone preparation; labeled hormone preparation

ELISA

Enzyme Linked ImmunoSorbent Assay

Steps of an ELISA

apply antibody to well plate; incubate; wash; cover with protein; wash; introduce hormone; wash; treat with marked antibody that will bind to hormone; treat with color producing substrate; color is produced if enzyme is present

northern blot

allows for bioassay via hormone RNA; permits determination of the size of the RNA

northern blot steps

fix tissue sample to slide; apply radiolabeled probe; hybridize; dip into emulsion; wash slides; develop and examine microscopically

reverse transcription steps

isolate RNA, addreverse transcriptase, make cDNA, design primers, go to town

Cell Surface Receptors

characterized by receptor: effector coupling by a G protein

protein/peptide hormone receptors

membrane spanning hormone receptors; single membrane spanning component can be with or without tyrosine kinase; 7 membrane spanning may either be coupled to a G protein or be part of an ion channel

adenylyl cyclase mediating hormones

beta adrenergic, LH, FSH, TSH, hCG, vasopressin, ACTH, vasopressin V2

phosphoinositide turnover mediating hormones

vasopressin V1

tyrosine kinase activation mediating hormones

GH, insulin, Prolactin

Steroid hormone receptors

classically intracellular; hormone passes through cell membrane and acts through a binding cascade to affect transcription

agonist

compound that acts like a hormone and binds to a receptor, activating it

antagonist

compound that binds to a receptor, blocking hormone response

receptor mediated endocytosis

mechanism by which hormone receptors are downregulated

second messenger

intrecellular molecule which carries out a hormones effects intracellularly; does what the hormones does. hormone stimulation increases conc. in cell

membrane receptor activation of adenylate cyclase

hormone binds, alpha subunit activates protein, ATP ultimately converted to cAMP

Activation of protein kinase a

performed by cAMP

cAMP inhibition

performed by alpha inhibitory subunits

adrenergic receptor mode of function

couples with G protein, activates alpha subunit, begins making cAMP, BetaARK phosphorylated BetaAR; deactivating and downregulating the receptor

heterologous desensitization

hormone "pool" lost with processing

Beta arrestin action

immediately desensitizes receptor; but also plays a role in long term mechanisms of extracellularly regulated kinases

phosphodiesterase inhibitors

methylxanthines (caffeine, tea stuff, chocolate stuff): overall result in to increase cAMP prevalence. acts as an endogenous epinephrine boots

protein kinase a function

phosphorylates and activates proteins

Phosphoinositide system

cell surface receptors; G protein linked. phospholipase C activated by PIP2, generating inositol triphosphate and diacylglycerol and activating protein kinase C

role of calmodulin

enhances the activity of protein kinase C

tyrosine kinase activators

generally long range effect hormones; MAPK, mitosis stimulating kinase

tyrosine kinase activity receptors

generally dimers; hormone binding causes conformational change in receptor which confers biological activity

smads

mediate TGFbeta family members

classes of serine, threonine kinase receptors

type 1 and type 2 homodimers and heterodimers

signalling mechanism of receptors with serine threonine kinase receptors

hormone binding to type II receptor, recruitment of type I receptor, phosphorylation of type I receptor. signalling only occurs when receptors are dimerized

smad 4

activation generally associated with transcription

significance of zinc fingers in steroid receptors

allows receptor to interpolate itself into DNA

location of steroid hormone receptors

associated with or in nucleus

gene transcription regulation by steroid receptors

receptor binds hormone, dissociated from complex with heat shock protein, binds upstream to target DNA, recruits coactivators

gene transcription regulation by thyroid receptors

inactive receptor sits on DNA and binds a repressor. Corepressor released following hormone binding and coactivator can be bound

estrogen receptors

classically tethered; different types transcribed from different genes

progesterone receptors

both isoforms derived from same gene but have different modes of action

adrenal medulla

contains chromafin tissue; part of the sympathetic nervous system

adrenal cortex

secretes steroid hormones

zona glomerulosa

outer layer of the adrenal cortex; controlled by renin-angiotensin. produces aldosterone

zona fasiculata

middle layer of the adrenal cortex; controlled by ACTH, produces cortisol

zona reticularis

inner layer of the adrenal cortex; controlled by ACTH, produces androgens

location of catecholamines (epinephrine)

adrenal medulla; tyrosine derived and influenced by cortisone

adrenal medullary product in response to stress

norepinephrine

relationship of alpha and beta adrenergic receptors

alpha dominates beta. beta generally stimulatory to cell secretion; alpha generally inhibitory

first step in steroid synthesis

cholesterol side chain cleaveage by Side Chain Cleavage enzyme (SCC)

Steriod Acutely Regulated protein (StAR)

cholesterol transporter functioning between inner and outer mitochondrial membranes

21 Hydroxylase

critical enzyme in aldosterone and cortisol production; deficiency is known as adrenal hyperplasia

control of the adrenal cortex

CRH stimulates ACTH-CRH; daily rhythm in plasma ACTH and cortisol

effects of hypovolemia

decreased plasma osmolarity, renin secretion, converts angiotensinogen to angiotensin I, converted to angiotensin II, stimulates zona glomerulosa to produce vasopressin

glucocorticoid influences on peripheral tissues

antiinflammatory, stabilizes lysosomal membranes, maintains normal blood pressure and kidney function, decreases histamine release, generally permissive

glucocorticoid influence on prostaglandins

inhibitory; prevents release of precursor molecule from lipids and decreases release of precursor molecules from lipids

atrial naturietic factor

stimulated by atrial distension, leads to natriuresis (salt excretion) and decreased renin production, angiotensin II, aldosterone and vascular resistance

Effects of ANP system

increases GFR; decreasing blood pressure and volume

function of thyroid gland

establishes a baseline metabolic rate; produces T4 and T3

parathyroid

glands involved in Calcium ion regulation

thyroid follicular cells

secrete T3 and T4

thyroglobulin

stored in thyroid lumen; iodine in incorporated in tyrosine residues to become thyroxine

thyroxine

fully iodized thyroglobulin; contains 4 iodines

T3 triiodo thyronine

biologically significant; acts with a shorter pathway than T4

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