Pulsatile luteinizing hormone and follicle-stimulating hormone secretion and gonadotropin subunit mRNA levels in the ovariectomized GPR-4 transgenic rat.
Genetic targeting of the cAMP-specific phosphodiesterase 4D1 (PDE4D1) to gonadotropin-releasing hormone (GnRH) neurons in the GPR-4 transgenic rat resulted in decreased luteinizing hormone (LH) pulse frequency in castrated female and male rats. A similar decrease in the intrinsic GnRH pulse frequency was observed in GT1 GnRH cells expressing the PDE4D1 phosphodiesterase. We have extended these findings in ovariectomized (OVX) GPR-4 rats by asking what effect transgene expression had on pulsatile LH and follicle-stimulating hormone (FSH) secretion, plasma and pituitary levels of LH and FSH, and levels of the alpha-glycoprotein hormone subunit (alpha-GSU), LH-beta and FSH-beta subunit mRNAs. In OVX GPR-4 rats the LH pulse frequency but not pulse amplitude was decreased by 50% compared to wild-type littermate controls. Assaying the same samples for FSH, the FSH pulse frequency and amplitude were unchanged. The plasma and anterior pituitary levels of LH in the GPR-4 rats were significantly decreased by approximately 45%, while the plasma but not anterior pituitary level of FSH was significantly decreased by 25%. As measured by real-time RT-PCR, the mRNA levels for the alpha-GSU in the GPR-4 rats were significantly decreased by 41%, the LH-beta subunit by 38% and the FSH-beta subunit by 28%. We conclude that in the castrated female GPR-4 rats the decreased GnRH pulse frequency results in decreased levels of LH and FSH and in the alpha- and beta-subunit mRNA levels.
El Majdoubi
Mohammed
M
Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA 94143, USA.
Paruthiyil
Sreenivasan
S
Weiner
Richard I
RI
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D005260:Female; D037201:Follicle Stimulating Hormone, beta Subunit / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics*; D037101:Luteinizing Hormone, beta Subunit / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D010052:Ovariectomy; D011673:Pulsatile Flow; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D037201:Follicle Stimulating Hormone, beta Subunit; D037101:Luteinizing Hormone, beta Subunit; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4