INDUCTION OF OVARIAN FOLLICLE LUTEINIZATION BY RECOMBINANT FOLLICLE-STIMULATING-HORMONE

Ovulation and subsequent luteal tissue formation are preceded by midcy cle surges of both LH and FSH. Although LH has been widely known as th e luteinizing hormone, a potential role for FSH in the luteinization p rocess is possible. Our earlier studies using recombinant FSH (rcFSH) without LH contamination have shown that treatment with a surge dose o f rcFSH induces ovulation of mature follicles in hypophysectomized rat s. The present studies examined further whether FSH alone is sufficien t to induce normal corpus luteum formation. Immature hypophysectomized rats were implanted with an estrogen pellet (10 mg diethylstilbestrol ). Two days later, a minipump releasing 4 IU rcFSH/day was placed to i nduce follicular growth. Forty-eight hours after FSH treatment, both D ES pellet and FSH minipump were removed, and rats were injected with a single sc dose of 40 IU rcFSH, 5 mug hCG, or saline. For some animals , oviducts were excised the following day to determine the number of o vulated oocytes. The remaining animals received, 2 days later, sc inje ctions of 125 mug ovine PRL twice daily for 3 days to maintain luteal function. All rats that received a surge dose of rcFSH or hCG ovulated similar numbers of oocytes, whereas none of the control animals did. Ovaries and blood samples were obtained 5 days after the gonadotropin surge. rcFSH and hCG significantly increased ovarian weight to 73.9 +/ - 4.8 and 94.7 +/- 5.6 mg, respectively, compared to 10.0 +/- 0.5 mg i n controls. Serum progesterone levels were increased by 192- and 102-f old in rcFSH- and hCG-treated animals, respectively, compared with tho se in the saline-treated rats. rcFSH and hCG also induced a marked ele vation of ovarian [I-125]hCG binding (4.2 +/- 0.2 and 3.7 +/- 0.1 ng/m g ovary, respectively), whereas ovaries from control animals exhibited low binding (0.6 +/- 0.1 ng/mg ovary). These gonadotropin-induced inc reases in [I-125]hCG binding were associated with similar elevations i n the levels of three LH receptor transcripts of 2.5, 4.2, and 7.0 kil obases. Also, levels of the ovarian cholesterol side-chain cleavage en zyme (CYP 11A) mRNA (2 kilobases) were low in control animals, but inc reased 20.5- and 14.3-fold after surge doses of rcFSH and hCG, respect ively. Accompanied by biochemical signs of luteinization, morphologica l features typical of luteinized ovaries were found in both rcFSH and hCG groups, showing the formation of large polyhedral lutein cells and small spindle-shaped lutein cells. These results demonstrate that rcF SH treatment alone is capable of inducing luteinization of follicular cells comparable to that induced by hCG, suggesting that the preovulat ory surge of FSH, like that of LH, may participate in the luteinizatio n process.