Hypothalamic-pituitary borders: thalamus (cranial); optic chiasm (rostral); sphenoid bone/sella turcica (caudal); mammillary body (dorsal)

 

Hypophysiotropic hypothalamic nuclei: POA (rostral; GnRH surge center) > median eminence; ARC (medial basal; GnRH tonic center) > median eminence; supraoptic/paraventricular (rostral; oxytocin) > posterior pituitary

 

Pituitary embryology: oral ectoderm (Rathke's pouch) > adenohypophysis (anterior lobe = pars distalis and tuberalis; intermediate lobe/pars intermedia); neural ectoderm (diencephalon) > neurohypophysis/pars nervosa/posterior lobe

 

Hypothalamic-pituitary portal system: superior hypophyseal artery > primary capillary plexus (median eminence) > portal vessels (infundibular stalk) > secondary capillary plexus (anterior pituitary) > venous return

 

Alterations in hypothalamic sensitivity to negative feedback dictate transitional states in breeding activities: during periods of nonbreeding (eg., prepuberal, seasonal, lactational, stress) the GnRH tonic center (ARC) is very sensitive to gonadal sex steroid feedback (testosterone in males, estradiol in females) - insufficient GnRH production results in low gonadotropin (FSH, LH) output and gonadal atrophy; during breeding conditions sensitivity to negative feedback is diminished and therefore adequate GnRH is produced to activate the pituitary-gonadal axis

 

GnRH: decapeptide; hypothalamus; anterior pituitary; gonadotropin production

PIF: dopamine; hypothalamus; anterior pituitary; inhibition of prolactin secretion

Oxytocin: nonapeptide; hypothalamus; uterus, mammary gland; myometrial (labor) and myoepithelial (milk let-down) contractions

Melatonin: indolamine (tryptophan > serotonin derivative); pineal gland; hypothalamus; seasonal rhythmicity of breeding activity

FSH/LH: gonadotropins/subunit glycoproteins; anterior pituitary; gonads; steroidogenesis (FSH > inhibin), gametogenesis

PMSG (eCG): gonadotropin/subunit glycoprotein; placenta; ovary; follicular growth, accessory CL (pregnancy) formation

hCG: gonadotropin/subunit glycoprotein; placenta; ovary; luteal maintenance during early pregnancy

Prolactin: protein; anterior pituitary; ovary, mammary gland, hypothalamus; luteotropin, milk synthesis, maternal behavior

Inhibin: subunit glycoprotein; gonads; anterior pituitary; inhibition of FSH secretion

Relaxin: two-chain polypeptide; ovary, placenta; uterus, pelvis; parturition (cervical/pelvic dilation)

MIH: homodimeric glycoprotein; fetal testis; Mullerian duct; regression of Mullerian duct (indifferent female reproductive tract) in the male embryo

Progesterone: sex steroid; ovary, placenta; brain, reproductive tract, mammary gland; negative feedback control of GnRH, behavior modification, preparation of tubular organs for pregnancy, mammary development

Testosterone: sex steroid; testis; brain, duct system, accessory glands, secondary organs; negative feedback control of GnRH, libido, maintenance of ducts, growth/secretory development of accessory glands, secondary sex characteristics (body condition, hair growth, voice, etc.)

Estradiol: sex steroid; ovary, placenta; brain, reproductive tract, mammary gland, secondary organs; negative and positive (preovulatory) feedback control of GnRH, estrous behavior, growth and contractility (gamete transport, labor) of tubular organs, mammary development, secondary sex characteristics

Cortisol: glucocorticoid; adrenal cortex; placenta; induction (steroidogenic [P4 > E2] shift) of parturition (farm animals)

 

Transcription: synthesis of mRNA from a template of complementary DNA

Translation: RNA-directed protein synthesis

Post-translational modification: intracellular processing of proteins (eg., hormones, receptors) into bioactive molecules (eg., enzymatic cleavage of a proform, folding, glycosylation, subunit assembly)

Cabergoline, Bromocryptine: ergot derivatives used as a dopamine agonist to inhibit prolactin secretion and prolactinomas (also suppress cell division)

NAT/HIOMT: enzymes that convert serotonin to melatonin

Receptor-mediated endocytosis: ligand (eg., LDL/cholesterol or hormone)-receptor coupling > complex clustering > internalization (endocytotic vesicles) > vesicle fusion (endosome) > endosome-primary lysosome fusion (secondary lysosome) > ligand delivery, receptor recycling

Paracrine: local mode of intercellular communication whereby a secreted substance acts on a neighboring cell

Autocrine: action of a secreted substance directly back upon its cellular site of origin

Catecholamine: a derivative of tyrosine (dopamine, norepinephrine, epinephrine); often act locally to modify hypothalamic-pituitary and gonadal responses

Histamine: a proinflammatory derivative of histidine; is involved in the local regulation of GnRH neurons and in the mechanics of (intrusive) implantation in some animals

Endogenous opiate: natural morphine-like compounds (eg., b-endorphin) that inhibit GnRH production (and thus mediate inhibitory effects of stress on reproduction)

Growth factor: local modulators of tissue differentiation

Cytokine: products of cells of the immune system; putative local regulators of reproductive processes

Calmodulin: calcium-binding protein; a mediator of intracellular transport, exocytosis, smooth muscle contraction, and cAMP production

RU 486: mifepristone; a competitive inhibitor of progesterone-receptor binding; an abortifacient

Accuracy: nearness to true

Precision: repeatability

Sensitivity: minimum detectable quantity

Specificity: ability to discriminate one compound from another

Scatchard plot: a graphic analytic technique used to evaluate receptor data (numbers, affinity)

 

Steroidogenic pathways: cholesterol (mitochondrial side-chain cleavage) > pregnenolone (hydroxylase) > 17a-hydroxypregnenolone (desmolase) > DHEA (dehydrogenase, isomerase) > androstenedione (dehydrogenase) > testosterone (aromatase) > estradiol [delta-5]; cholesterol > pregnenolone (dehydrogenase, isomerase) > progesterone [delta-4]

Progestogens = C-21 steroid hormones (pregnenolone, progesterone, 17a-hydroxy intermediates)

Androgens = C-19 steroid hormones (DHEA, androstendione, testosterone)

Estrogens = C-18 steroid hormones (estrone, estradiol, estriol)

 

End-products of steroid metabolism: hepatic inactivation is by saturation and conjugation (water solubility); however, some peripheral metabolites can possess potent biological activity (eg., aromatization or 5a-reduction of testosterone to estradiol or DHT, respectively)

 

Eicosanoid biosynthesis: arachidonate > PGs, TXs (cyclooxygenase pathway - inhibited by NSAIDs); arachidonate > LTs, LXs (lipoxygenase pathway)

Primary roles of prostaglandins in reproduction: luteolysis (PGF2a), parturition

 

Gonadotropin receptors: single-chain glycoproteins with a hormone (b subunit specificity)-binding exodomain, signal transduction (a subunit interaction) seven-transmembrane loop region, and C-terminal tail

Steroid hormone receptors: are localized within the nuclear matrix; contain (hydrophobic) hormone- and DNA-binding domains

 

cAMP second-messenger system (membrane receptor model): protein hormone-receptor coupling > Gs (transducer protein) + GTP > adenyl cyclase activation > ATP > cAMP > protein kinase (A) activation > phosphorylation of membrane and nuclear proteins > secretory events, genomic expression

Negative controls: phosphodiesterase; GTPase activity of Gs; Gi; internalization of hormone-receptor complexes; phosphoprotein phosphatases; calcium efflux

Intracellular receptor model: steroid hormone diffusion > binding to nuclear receptor > dissociation of HSP > DNA interaction > transcription

 

PIP2 hydrolysis > inositol triphosphate (cytosolic), diacylglycerol (membrane)

 

RIA theory: radioactive tracer and standard hormone compete for binding sites on complementary antibodies > amount of (separated) radiolabel bound (Y axis) declines with increasing concentrations of standard (X axis); unknown (sample) values are derived from the standard curve

Advantage of ELISA: no radioactivity; enzyme-antibody conjugate used for hormonal detection (substrate > product)


PUZZLE: grid, clues, solution.