PHRM 825 Lecture 15- Pituitary Hormones I

what hormones are released by the hypothalamus

GHRH, TRH, CRH, GnRH

what hormones are released by the anterior pituitary

GH, TSH, ACTH, LH, FSH

what hormones are released by the posterior pituitary

ADH and oxytocin

stimulates release of FSH and LH

gonadotropin-releasing hormone (GnRH)

single chain protein hormones

associated with JAK/STAT pathway

growth hormone, prolactin

dimeric protein hormones sharing common alpha chain

activate GPCRs

B chain confers receptor specificity

TSH, FSH, LH

single chain peptide

activates GPCR

adrenocorticotropic hormone (ACTH)

action of FSH in women and men

women: directs ovarian follicle development, stimulates conversion of testosterone to estrogens

men: spermatogenesis, conversion of testosterone to estrogens

action of LH in women and men

women: stimulates androgen production in follicular phase, controls estrogen and progesterone production in luteal phase

men: stimulates androgen production

produced in placenta during pregnancy

identical with LH

controls estrogen and progesterone during pregnancy

hCG

preparations used clinically

menotropins, urofollitropin (uFSH), follitropin a and follitropin B, lutropin a, hCG, rhCG

human menopausal gonadotropin

first commercial gonadotropin

extracted from urine of postmenopausal women

mixture of FSH and LH

menotropin

FSH purified from urine of postmenopausal women, LH activity removed

urofollitropin (uFSH)

recombinant forms of FSH, differ from each other and uFSH in carbohydrates chain

more expensive that uFSH

follitropin a and follitropin B

recombinant form of LH

used in combination with follitropin a for stimulation of follicular development in infertile women

lutropin a

extracted from urine of pregnant women

hCG

recombinant form of hCG

Choriogonadotropin a (rhCG)

clinical uses of preparations

ovulation induction

controlled ovarian hyperstimulation for IVF

male infertility

adverse effects of using synthetic gonadotropin preparations

ovarian hyperstimulation syndrome

multiple pregnancy

hormone secreted by neurons in the hypothalamus

binds to GPCRs on membrane of cells in the anterior pituitary

GnRH

acetate salt of synthetic human GnRH

very short half life

gonadorelin

synthetic analogs of GnRH

goserelin, histrelin, leuprolide, nafarelin, triptorelin

effects of pulsatile vs nonpulsatile GnRH administration

pulsatile: stimulates release of LH and FSH

nonpulsatile: inhibits the release of FSH and LH in women and men

clinical use of pulsatile GnRH administration

female and male infertility- stimulate pituitary to release FSH and LH

clinical use of nonpulsatile GnRH administration

controlled ovarian hyperstimulation

endometriosis

prostate cancer

central precocious puberty

what are the GnRH receptor antagonists

Ganirelix

Cetrorelix

Degarelix

Abarelix

use of GnRH antagonists

controlled ovarian hyperstimulation (immediate effect --> shorter duration of treatment)

advanced prostate cancer