Leptin induces ovulation in GnRH-deficient mice.
Leptin-deficient ob/ob mice have reduced gonadotropin-releasing hormone (GnRH) secretion, leading to gonadotropin deficiencies, hypogonadism, and anovulation, which are completely reversed following leptin administration. To determine whether the role of leptin in ovulation is mediated exclusively through GnRH, we studied leptin's action in GnRH-deficient (hpg) mice, as well as ob/ob mice and normal, prepubertal mice in which the GnRH axis was blocked with antide. Following pretreatment with pregnant mare serum gonadotropin, leptin induced ovulation in all three mouse models. Unlike mature normal mice, these ovulations were not triggered by a luteinizing hormone (LH) surge, as demonstrated by lack of increase in its surrogate marker progesterone. Rather, leptin induced hyperemia and leakage in the follicle, as well as the proteinase ADAMTS-1 (a disintegrin and metalloproteinase with a thrombospondin-like motif), which facilitates extrusion of the follicular content. These data show that on top of its role as an inducer of GnRH secretion, leptin may elicit an LH-independent ovulation.
Barkan
Dalit
D
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
Hurgin
Vladimir
V
Dekel
Nava
N
Amsterdam
Abraham
A
Rubinstein
Menachem
M
D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; D000818:Animals; D003338:Corpus Luteum / Q000254:growth & development; D019483:Disintegrins / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000172:deficiency*; D006064:Gonadotropins, Equine / Q000494:pharmacology; D007006:Hypogonadism / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology*; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes / Q000378:metabolism; D006080:Ovarian Follicle / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D010060:Ovulation / Q000097:blood / Q000187:drug effects*; D011374:Progesterone / Q000097:blood
D019483:Disintegrins; D006064:Gonadotropins, Equine; D020738:Leptin; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C486323:Adamts1 protein, mouse; D008666:Metalloendopeptidases