2. therio- female repro review

what is the key regulator of the reproductive axis?

GnRH (gonadotropin releasing hormone)

what is GnRH?

gonadtotropin releasing hormone- a decapeptide synthesized by neurons in the hypothalamus

stimulates LH and FSH secretion in anterior pituitary via the portal system

what is the purpose of pulsatile secretion of GnRH?

pulsatile nature of GnRH release prevents receptor refractoriness (down-regulation)

what does the pulsatile secretion of GnRH determine?

determines the pattern of secretion of the gonadotropins FSH and LH, which then regulate both the endocrine function and gamete maturation in the gonads

decreasing low frequency= FSH secretion

increasing high frequency= LH secretion (1/hr)

how does the kisspeptin-neurokinin-dynorphin (KNDy) neuronal network in the hypothalamus control GnRH secretion?

KNDy mediates both positive and negative sex steroid feedback control of GnRH secretion in conjunction with other neuropeptides and neurotransmitters

which hormones decrease secretion of GnRH?

progesterone, CRH, and ACTH decrease secretion of GnRH

estrogen has a biphasic effect on GnRH release

how does melatonin influence GnRH secretion?

via RFamide related peptides

how do the affects of melatonin on GnRH secretion differ in short-day vs. long-day breeders?

long day breeders (such as horses) melatonin is inhibitory to GnRH secretion

short day breeders (such as sheep) melatonin is stimulatory to GnRH release

what is kisspeptin?

peptide released by Kiss1 neurons (AVPV and ARC) in hypothalamus, which acts directly on GnRH neurons in the hypothalamus to stimulate GnRH release

what do mutations in kisspeptin lead to?

mutation in kisspeptin makes it ineffective, leading to hypogonadotropic hypogonadism (inhibiting gonads from making sex hormones)

how is kisspeptin controlled?

through various metabolic factors:

1. negative feedback directly from gonadal sex steroids (estradiol/testosterone)

2. positive feedback directly from RF-amide related peptides

is dynorphin stimulatory or inhibitory to kisspeptin release?

inhibitory

is Neurokinin B stimulatory or inhibitory to kisspeptin release?

stimulatory

where and when is melatonin synthesized and secreted?

synthesized and secreted by the pineal gland during periods of darkness

detection via photoreceptors in retina

-receptors also present in hypothalamus and pituitary

what is oxytocin? where is it synthesized?

a nonapeptide, synthesized by neurons in the hypothalamus

also synthesized by the ovary (CL), testis and adrenal gland

where is oxytocin released?

released by the posterior pituitary

what stimulates release of oxytocin?

release is stimulated by suckling or cervical pressure

what are the functions of oxytocin?

-induces milk ejection

-elicits maternal behavior

-induces myometrial contractility

-stimulates prolactin release

-stimulates PGF2-alpha secretion from endometrium (only if oxytocin receptors are present, which come from estradiol in CL)

where is prolactin secreted?

by anterior pituitary (lactotropes)

what stimulates prolactin secretion?

thyrotropin releasing hormone (TRH) and oxytocin (OT)

what inhibits prolactin secretion?

dopamine (D2 receptor)

--> ergoalkaloids act as D2 receptor agonists to suppress prolactin secretion (can cause prolonged gestation in mares)

where is relaxin secreted?

secreted by the placenta, CL, uterus

what is the function of relaxin?

-decreases tissue collagen content of pelvic ligaments, cervix, vulva

-inhibits uterine contractility

-important for mammary gland development

can be used clinically as a pregnancy test

how do the glycoproteins FSH, LH, eCG, hCG, inhibin, activin, and TSH differ structurally? how are they similar?

all share the same alpha-subunit (~90 AA)

they differ in the beta-subunit, giving them each biologic specificity

where is inhibin secreted?

secreted by the ovary (granulosa cells) and testis (sertoli cells)

what is the function of inhibin?

inhibits FSH synthesis and secretion (negative feedback) and decreases GnRH receptor sensitivity

-potentially used for superovulation

where is FSH secreted?

secreted by pituitary gonadotropes

what is the function of FSH?

necessary for follicle development in the ovary by binding granulosa cells up until pre-ovulation, which then becomes a negative feedback hormone to suppress further FSH release from pituitary

where is LH secreted?

secreted by pituitary gonadotropes

what is the function of LH?

-necessary for follicle maturation and ovulation

-mediates CL formation and maintenance

-stimulates androgen secretion which is aromatized to estradiol

how is LH secretion controlled?

1. indirect negative feedback from sex steroids and FSH

2. weak negative feedback from estradiol (when binding estrogen2-alpha)

3. strong positive feedback from estradiol (when binding estrogen2-beta)

how does FSH and LH work together to promote estrogen formation?

granulosa cells and thecal cells bind LH

-LH promotes androgen formation in thecal cells (androgens freely moce into granulosa cells)

-LH and FSH together binding to granulosa cells to convert the androgens into estrogen, which is them released into bloodstream

-release further stimulates follicles to produce more FSH and LH receptors

how is FSH secretion controlled?

1. via direct negative feedback on the hypothalamus and anterior pituitary

2. inhibins produced by maturing follicle suppress FSH production and secretion in anterior pituitary

what is eCG? where is it secreted?

equine chorionic gonadotropin, secreted by the endometrial cups on the placenta of horses beginning at day 40 to day 100 of gestation

what is the function of eCG in equids?

it is luteotropic in mares (acts like LH):

-maintenance of primary CL

-formation of secondary CLs

what is the function of eCG in other species?

eCG in other species has FSH-like qualities, used for superovulation

what is hCG? where is it secreted?

human chorionic gonadotropin

secreted by human trophoblast beginning 2 weeks post fertilization, it's important for CL maintenance in humans

what is the function of hCG in domestic animals?

hCG has LH-like activity in domestic animals:

-used to induce ovulation

-stimulates androgen secretion in males

what is the major source of estrogens? what are other sources?

major source: ovarian follicles

other sources: CL, placenta, fetal gonads, adipose tissue (converts androstendione to estradiol)

what are the functions of estrogens?

responsible for behavioral signs of estrus and mammary gland development

increases synthesis of GnRH receptors

how do estrogens increase synthesis of GnRH receptors?

1. increases LH secretion (LH surge) and ovulation

2. in conjunction with inhibin, decreases FSH

where are progestins (progesterone) produced?

progestins are produced by granulosa cells before ovulation:

-luteinized following ovulation

-develop into CL; both thexa derived and granulosa derived luteal cells produce progesterone

what are the functions of progesterone?

-decreases GnRH pulse frequency

-necessary for endometrial gland secretion and lactogenesis

-promotes alveolar development in the mammary gland

where is PGF2-alpha (prostaglandin) produced?

produced by the endometrium of cycling females unless maternal recognition of pregnancy occurs

in lesser amounts, produced by the CL

what is the function of prostaglandins?

-causes luteolysis

-increases myometrial and myosalpinx contractility (enhances uterine clearance)

what hormone increases endometrial synthesis of PGF2-alpha?

oxytocin