Prolonged stimulation by follicle-stimulating hormone is required for the induction of ovarian follicular cysts by human chorionic gonadotropin in hypophysectomized rats

Abstract

Combined stimulation by follicule-stimulating hormone (FSH) and subovulatory doses of human chorionic gonadotropin (hCG, luteinizing hormone [LH]-like activity) produces large ovarian follicular cysts in hypophysectomized (HYPOXD) immature rats. To obtain a better understanding of the extent to which stimulation by FSH is required in order for hCG to induce these ovarian cysts, immature HYPOXD rats were given subcutaneous (sc) injections of 1 IU hCG twice daily for 9 d, either alone or with daily injections of 2 μg of highly purified ovine FSH on 1. Day one of hCG treatment; 2. Days one and two of hCG treatment; 3. Days one through five of hCG treatment; or 4. All 9 d of hCG treatment. Ovaries and serum samples were collected on the morning of d 10 of treatment. Animals that were treated for 9 d with hCG, but that received either no FSH or only 1 or 2 d of FSH treatment, did not display antral follicles on day 10 of treatment. The largest cross-sectional areas for the ovaries from animals that received 1 or 2 d of FSH treatments ranged between 6.84±0.51 mm(2) and 8.94±0.89 mm(2). The diameters of the largest preantral follicles in the ovaries of these two groups ranged between 0.278±0.011 and 0.320±0.028 mm, respectively. In contrast, ovaries from hCG-treated HYPOXD rats that received FSH treatments for either 5 or 9 d displayed follicular cysts by the morning of day 10. The largest cross-sectional areas for the ovaries from these two treatment groups were similar (15.68±1.61 and 18.7±5.13 mm(2), respectively), as were the mean diameters of the cystic follicles in these two groups (0.929±0.096 and 0.830±0.063 mm, respectively). Although serum androstenedione and testosterone concentrations were greater for HYPOXD rats that received combined FSH+hCG treatments than for animals that received hCG treatments alone, these concentrations did not increase with increasing numbers of days of FSH treatment. As with serum androstenedione and testosterone concentrations, serum estradiol and estrone concentrations for HYPOXD rats treated with hCG alone were limited (0.002±0.001 and 0.004±0.002 ng/mL, respectively), but had increased by day 10 after a single injection of FSH on day one of treatment. In contrast to serum androgen concentrations, serum estradiol and estrone concentrations continued to increase as the number of days of combined FSH+hCG treatment increased. These observations indicate that, in the rat, a significant period of exposure to tonic stimulation by both FSH and LH-like activity is required for the development of large ovarian cysts. Further, this period of exposure to FSH appears to be linked to increased peripheral serum estrogen concentrations, rather than to increased androgen concentrations. Therefore, the data provide indirect support for the concept that estrogens play a direct role, at the level of the ovary, in the induction of large ovarian cysts in the rat.