The effect of Nestorone on gonadotropic cells in pituitary of rats.
The implant containing Nestorone is a promising long-acting contraceptive especially suitable for lactating women. In this study, two experiments were designed to observe the effect of Nestorone on the gonadotropic cells in pituitary of rats for analyzing its antiovulation mechanism. In the first experiment, the ED50 of Nestorone on inhibiting ovulation was found to be 1.32 mg/kg. The serum luteinizing hormone (LH) levels were significantly lower 60 h after being treated with Nestorone at 8:30-9:00 a.m. on Day 2 (D2) of estrus. Image analysis showed that the average size of the LH cells in groups treated with Nestorone at 2 or 4 mg/kg was larger than that of the control. In the group treated with 4 mg/kg, most of gonadotropic cells were regular round in shape. And, abundant granules in cytoplasm were found in those cells, which indicated that the LH stored in cells was not released. In the second experiment, the rats were treated with Nestorone at 5 mg/kg at 11:30-12:00 a.m. on D2 of estrus. The normal or higher expression of LHbeta mRNA in pituitary suggested that the synthesis of LH was not inhibited by the treatment with Nestorone. The expression of PR mRNA in pituitary was significantly lower than that of the control at 33 h after treatment. This might be a direct effect of Nestorone, since there were no differences in the serum E2 and P4 levels between the treated and the control group. It is concluded that Nestorone prevents ovulation through inhibition of LH secretion and it has no effect on synthesis of LH. Progesterone receptors in pituitary might be involved in this process, but further study is needed to gain more evidence.
Zhao
Xiao-Feng
XF
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing.
Xu
Yan-Qun
YQ
Wang
Yan-Ling
YL
Leng
Ying
Y
Cao
Lin
L
Jin
Jing-De
JD
Gu
Zhi-Ping
ZP
D000818:Animals; D003271:Contraceptive Agents, Female / Q000494:pharmacology*; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants / Q000494:pharmacology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000097:blood / Q000187:drug effects / Q000235:genetics; D037101:Luteinizing Hormone, beta Subunit / Q000097:blood / Q000187:drug effects / Q000235:genetics; D009653:Norprogesterones / Q000494:pharmacology*; D010060:Ovulation / Q000187:drug effects*; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011980:Receptors, Progesterone / Q000097:blood / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D003271:Contraceptive Agents, Female; D017931:DNA Primers; D004343:Drug Implants; D037101:Luteinizing Hormone, beta Subunit; D009653:Norprogesterones; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D007987:Gonadotropin-Releasing Hormone; C029167:ST 1435