Divergent effects of gonadotrophin-releasing hormone (GnRH) analogue and authentic GnRH on the anterior pituitary gland of rats with restricted feeding

Abstract

The effects of gonadotrophin-releasing hormone analogue (GnRHa; buserelin) on the pituitary function and morphology of food-restricted rats were compared with those of authentic GnRH. After adult female rats had been restricted to 10 g food/day for 60 days, various doses of GnRHa (10 ng, 100 ng and 1 microgram) or GnRH (10 micrograms) were administered either daily for 7 days or twice a week for 4 weeks from day 61 of the period of underfeeding. Underfeeding brought about a decrease in the pituitary gonadotrophin content, serum levels of gonadotrophins and oestradiol, and the number and size of both LH- and FSH-positive pituitary cells. Daily and/or twice-weekly administration of authentic GnRH to underfed rats produced an increase in pituitary and serum gonadotrophin levels and the number and size of both LH- and FSH-positive pituitary cells. The administration of GnRHa daily for 7 days increased serum gonadotrophin levels, while it produced a reduction in the pituitary gonadotrophin content and number and size of both LH- and FSH-positive pituitary cells in a dose-dependent manner. Twice-weekly administration of GnRHa also produced an elevation of serum gonadotrophin levels and reduction of pituitary gonadotrophin content, although it did not affect the numbers and areas of LH- and FSH-positive pituitary cells. A GnRH loading test performed after the GnRHa treatment showed that the GnRHa treatment performed in this study did not produce down-regulation of the GnRH receptor. Thus, it can be concluded that the gonadotrophin-synthesizing activity of GnRHa is weaker than that of authentic GnRH, or that GnRHa may preferentially exert gonadotrophin-releasing activity rather than gonadotrophin-synthesizing activity in the anterior pituitary of underfed rats.