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Differential Regulation of Gonadotropin Subunit Gene Expression by Gonadotropin-Releasing Hormone Pulse Amplitude in Female Rats

Department of Internal Medicine, University of Michigan Ann Arbor, Michigan 48109

Address requests for reprints to: Dr. John C. Marshall, University of Michigan Medical Center, Department of Internal Medicine, Division of Endocrinology and Metabolism, 1500 East Medical Center Drive, 3920 Taubman Center, Box 0354, Ann Arbor, Michigan 48109-0354.

Abstract

The role of GnRH in regulating gonadotropin subunit gene expression was examined in adult female rats. Animals were ovariectomized, estradiol implants inserted sc, and jugular cannulae placed into the right atria. On the next day, animals were given GnRH pulses (saline to controls) every 30 min for up to 48 h and a, LH β, and FSH/8 mRNA levels measured by hybridization to cDNA probes. To determine the effects of GnRH treatment duration, rats received GnRH pulses (25 ng at 30-min intervals) for 6, 12, 24, and 48 h. FSHβ mRNA was increased (by 92%) after 6 h of pulses and remained elevated through 48 h. a mRNA was not increased until 12 h (27% increase) and rose further (57%) by 48 h. LH β mRNA levels were only transiently increased at 12 h (67%) and values were not different from saline controls after 24 or 48 h. To examine whether the rise in serum PRL which is characteristic of the ovariectomized-estradiol animal model was responsible for the decrease in LH 0 mRNA responsiveness to GnRH over longer durations, studies were repeated in bromocriptine-treated animals (0.6 mg sc, twice daily). The results showed similar response patterns for all three subunit mRNAs including the decrease in LH β after 48 h. A third experiment examined the effect of varying GnRH pulse amplitude (0.5–250 ng/pulse at 30-min intervals) over 12 h. a mRNA levels were increased by all GnRH doses greater than 5 ng with maximum responses after 250 ng pulses. LH and FSH β mRNAs were both elevated by GnRH pulse doses of 0.5–25 ng (P > 0.05 vs. saline controls). Maximal increases (2-fold) were seen after 5 ng pulses for LH β and after 15-ng pulses for FSH β mRNA. These results show that pulsatile GnRH increases FSHβ mRNA more rapidly than a or LH β mRNAs in female rats. In addition, high amplitude GnRH pulses increase only a mRNA, whereas both LH β and FSH β mRNAs show maximum responses to lower doses. The data suggest that alterations in the amplitude of the GnRH pulsatile signal can exert differential effects on gonadotropin gene expression. (Endocrinology 127: 2869–2875, 1990)

Received May 3, 1990.

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