Control of gonadotropin secretion by follicle-stimulating hormone-releasing factor, luteinizing hormone-releasing hormone, and leptin.
Fractionation of hypothalamic extracts on a Sephadex G-25 column separates follicle-stimulating hormone-releasing factor (FSHRF) from luteinizing hormone-releasing hormone (LHRH). The FSH-releasing peak contained immunoreactive lamprey gonadotropin-releasing hormone (lGnRH) by radioimmunoassay, and its activity was inactivated by an antiserum specific to lGnRH. The identity of lGnRH-III with FSHRF is supported by studies with over 40 GnRH analogs that revealed that this is the sole analog with preferential FSH-releasing activity. Selective activity appears to require amino acids 5-8 of lGnRH-III. Chicken GnRH-II has slight selective FSH-releasing activity. Using a specific lGnRH-III antiserum, a population of lGnRH-III neurons was visualized in the dorsal and ventral preoptic area with axons projecting to the median eminence in areas shown previously to control FSH secretion based on lesion and stimulation studies. Some lGnRH-III neurons contained only this peptide, others also contained LHRH, and still others contained only LHRH. The differential pulsatile release of FSH and LH and their differential secretion at different times of the estrous cycle may be caused by differential secretion of FSHRF and LHRH. Both FSH and LHRH act by nitric oxide (NO) that generates cyclic guanosine monophosphate. lGnRH-III has very low affinity to the LHRH receptor. Biotinylated lGnRH-III (10(-9) M) labels 80% of FSH gonadotropes and is not displaced by LHRH, providing evidence for the existence of an FSHRF receptor. Leptin has equal potency as LHRH to release gonadotropins by NO. lGnRH-III specifically releases FSH, not only in rats but also in cows.
McCann
S M
SM
Department of Basic Science, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808-3030, USA. mccannsm@pbrc.edu
Karanth
S
S
Mastronardi
C A
CA
Dees
W L
WL
Childs
G
G
Miller
B
B
Sower
S
S
Yu
W H
WH
D000818:Animals; D002024:Bufo marinus; D002352:Carrier Proteins / Q000187:drug effects / Q000502:physiology; D002417:Cattle; D002645:Chickens; D003429:Cross Reactions; D005260:Female; D005326:Fetal Proteins / Q000032:analysis; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000502:physiology; D006065:Gonadotropins, Pituitary / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D000882:Haplorhini; D006728:Hormones / Q000302:isolation & purification / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D007031:Hypothalamus / Q000737:chemistry / Q000378:metabolism; D007106:Immune Sera; D007375:Interleukin-1 / Q000494:pharmacology; D007798:Lampreys; D020738:Leptin / Q000494:pharmacology* / Q000502:physiology; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D009842:Oligopeptides / Q000302:isolation & purification / Q000494:pharmacology* / Q000502:physiology; D006080:Ovarian Follicle / Q000187:drug effects; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011817:Rabbits; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D054411:Receptors, Leptin; D012636:Secretory Rate / Q000187:drug effects; D012726:Sexual Behavior, Animal / Q000187:drug effects / Q000502:physiology
D002352:Carrier Proteins; C448023:FSH-RF receptor; D005326:Fetal Proteins; D006065:Gonadotropins, Pituitary; D006728:Hormones; D007106:Immune Sera; D007375:Interleukin-1; C515448:LEPR protein, human; D020738:Leptin; D009842:Oligopeptides; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; C448022:gonadotropin-releasing hormone-III; D009569:Nitric Oxide; D007987:Gonadotropin-Releasing Hormone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C047717:LHRH, His(5)-Trp(7)-Tyr(8)-; D011761:Pyrrolidonecarboxylic Acid