Reduction of the amplitude of preovulatory LH and FSH surges and of the amplitude of the in vitro GnRH-induced LH release by substance P. Reversal of the effect by RP 67580.
The effects of Substance P (SP) and of a specific nonpeptide antagonist of the NK1 receptor (RP 67580) on preovulatory gonadotropin surges and on the in vitro GnRH induced LH surge were investigated in cycling female rats. A subcutaneous injection of SP (0.5 mg/kg body weight) at 12.00 h on the proestrous day significantly decreased the LH preovulatory surge. RP 67580 (1.5 mg/kg) significantly increased this LH surge. However, when SP and its antagonist were administered together, LH preovulatory surge was normal. The FSH preovulatory surge at 18.00 h and also at 19.00 h was significantly inhibited by SP administration. RP 67580 alone had no effect on the FSH preovulatory surge. When SP and RP 67580 were both administered, there was no diminution of FSH plasma levels at 18.00 h and 19.00 h. In vitro perifusions of anterior pituitaries showed that SP inhibits GnRH-induced LH release via a NK1 receptor. Thus, SP inhibits the LH preovulatory surge via NK1 receptors and SP modulation of gonadotropin surges is at least partly exerted at the pituitary.
Duval
P
P
Laboratoire de Neuroendocrinologie, CNRS URA 1310, Faculté des Sciences Pharmaceutiques et Biologiques-4, Paris, France.
Lenoir
V
V
Garret
C
C
Kerdelhue
B
B
D000704:Analysis of Variance; D000818:Animals; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D054833:Isoindoles; D007700:Kinetics; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D064729:Neurokinin-1 Receptor Antagonists; D011359:Proestrus; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone