The Development of Steroidogenic Capability and Responsiveness to Gonadotropins in Cultured Neonatal Rat Ovaries*

Abstract

The role of gonadotropins (LH and FSH) and steroid hormones [testosterone (Te) and 17β-estradiol (E₂)] in the development of ovarian steroidogenic capability and responsiveness to gonadotropins was studied in ovaries from 4-day-old rats maintained for 8–12 days in culture. Ovaries cultured in medium without hormonal supplementation produced small and decreasing amounts of steroids [progesterone (P) and E₂] during culture in spite of continued morphological development. The addition of LH (1 or 10 μg/ml) did not enhance P production during the first 4 days of culture but significantly stimulated it during days 4–8 of culture. FSH (0.5 μg/ml), Te (1 μg/ml), and E₂ (1 μg/ml) had no effect on their own, but when FSH or Te was added together with LH, P production during days 4–10 of culture was greatly enhanced. The acquisition of ovarian responsiveness to LH, as expressed by increased P production in response to the hormone, was achieved after 4–8 days of culture even without supplementation of the medium with LH before challenge. Dibutyryl cAMP caused an enhancement in P accumulation, first evident after 8–16 h of culture; after 96 h, the rate was 100 times higher than that induced by FSH plus LH. Production of E₂ was slightly enhanced by LH during days 4–10 of culture. FSH had no effect on its own but augmented the effect of LH. The addition of Te on its own significantly stimulated E₂ production even during the first 2 days. This effect of exogenous Te was greatly enhanced by FSH. Dibutyryl cAMP was also effective in inducing E₂ formation and greatly augmented the ability to convert Te to E₂ in the cultured neonatal ovaries. The results obtained permit the following conclusions: 1) steroidogenesis can be stimulated by cAMP in neonatal rat ovaries before sensitivity to LH is attained; 2) the ability to convert Te to estrogen can be augmented by FSH by the fourth day of postnatal life; 3) the ability of the neonatal ovary to respond to LH appears to be acquired by an autonomous developmental process and is expressed by the eighth day post parturn; and 4) once sensitivity to gonadotropins is established, steroidogenesis is controlled by an interplay of gonadotropins and steroid hormones. (Endocrinology106: 98, 1980)