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Downregulation of Follicle-Stimulating Hormone (FSH)-Receptor Messenger RNA Levels in the Hamster Ovary: Effect of the Endogenous and Exogenous FSH¹

Departments of Physiology and Biophysics³ Obstetrics and Gynecology,⁴ University of Nebraska Medical Center, Omaha, Nebraska 68198-4515

Although gonadotropins have been reported to downregulate FSH-receptor (FSHR) mRNA levels in the ovaries of female rats, the effect of the gonadotropin surge, particularly FSH, on hamster follicular FSHR mRNA levels warrants further examination. The objectives of the present study were to clone and determine the complete FSHR cDNA sequence of the hamster and to delineate the effects of endogenous and exogenous FSH on the steady-state levels of ovarian FSHR mRNA. Complete FSHR cDNA was derived from hamster ovarian total RNA by the strategy of 3'- and 5'-rapid amplification of cDNA ends. Ovaries were obtained before and after the endogenous gonadotropin surge or exogenous FSH administration, and the steady-state levels of FSHR mRNA were assessed by Northern blot hybridization. Cloned FSHR cDNA consists of a reading frame corresponding to exons 1–10 of the human FSHR gene and the 5'- and 3'-untranslated regions. The nucleic acid and amino acid sequences of the reading frame were at least 87% and 92% identical, respectively, to that of human, rat, and mouse FSHR. Furthermore, the amino acid sequence contained seven transmembrane domains characteristic of the FSHR. The steady-state levels of FSHR mRNA increased from estrus (Day 1) to reach a peak on proestrus (Day 4) noon; however, significant attenuation was noted following the gonadotropin surge, which was blocked by phenobarbital. Exogenous FSH also downregulated, both dose- and time-dependently, ovarian FSHR mRNA levels. These data indicate that the nucleic acid sequence of hamster FSHR has been identified and that FSH modulates FSHR mRNA levels in the hamster ovary.

¹ Supported by grants HD28165 and HD38468 from the National Institute of Child Health and Human Development (NICHHD, NIH) to S.K.R. The full-length cDNA sequence of the hamster FSH receptor has been deposited in the GenBank (accession no. AY509907).

² Correspondence: Shyamal K. Roy, Departments of OB/GYN and Physiology and Biophysics, DRC 5013, University of Nebraska Medical Center, Omaha, NE 68198-4515. FAX: 402 559 6164; skroy{at}unmc.edu

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