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Regulation of rat ovarian gonadotropin Releasing hormone receptor mRNA levels Väänänen, Céline Claire Magali

Abstract

The studies undertaken herewithin sought to characterize the pattern of regulation of the gonadotrophin-releasing hormone receptor (GnRH-R) mRNA levels in the rat ovary. The demonstration of gonadotrophin-releasing hormone (GnRH) transcripts in steroidproducing and steroid-dependent tissues suggests that GnRH may be implicated in the modulation of steroid action in those target tissues. Expression of GnRH-R mRNA increases in gonadal tissues and the pituitary with age, supporting the concept of GnRH as a local regulator in the developing rat as well as in the adult. During the peri-ovulatory period, stimulation of the ovarian luteinizing hormone receptor (LH-R) by an ovulatory dose of human chorionic gonadotrophin (hCG) is capable of inducing a transient and pronounced decrease in GnRH-R mRNA levels, thus bringing more evidence to the role of GnRH in the regulation of ovarian function during ovulation. The gene encoding GnRH-R was found to be expressed in granulosa cells. In a follicle stimulating hormone (FSH) pre-treated granulosa cell model, GnRH-R gene transcript levels were negatively influenced by LH, but not FSH, in a time- and concentration-dependent manner. Autostimulation of GnRH-R by GnRH was also seen. In a second granulosa cell model obtained from pregnant mare serum gonadotrophin (PMSG) synchronized immature rats, the levels of GnRH-R transcripts were found to be positively regulated by hCG and GnRH, while prostaglandin F2a (PGF20;) inhibited GnRH-R mRNA levels in a bell curve-like fashion. However, combinations of these treatments canceled each other's effects. In this model, GnRH stimulated progesterone (P4) production and only slightly inhibited hCG-stimulated progesterone production. This modulation in the responses to GnRH and in the levels of GnRH-R mRNA suggest that GnRH may have different actions at different times of follicular development. In conclusion, the findings of the present study demonstrate wide spread expression of the GnRH-R gene in steroidogenic or steroid-dependent tissues. Gonadotrophin-releasing hormone receptor mRNA levels were shown to be regulated by gonadotrophins, PGF2a and GnRH in the whole ovary and in granulosa cells, strongly supporting the postulated role of GnRH-R in the local modulations of ovarian function mediated by GnRH.

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