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Féral C, Le Gall S, Leymarie P. Angiotensin II modulates steroidogenesis in granulosa and theca in the rabbit ovary: its possible involvement in atresia. Eur J Endocrinol 1995;133:747–53. ISSN 0804–4643 Accumulating evidence has shown the ovary of mammals to contain an intrinsic renin–angiotensin system that has been ascribed an autocrine-paracrine role. The present study in the female rabbit ovary investigated the putative in vitro action of angiotensin II (A II) on basal and gonadotropin-induced steroidogenesis. Ovarian follicles from immature female rabbits treated with pregnant mare's serum gonadotropin (PMSG) were dissected out and a complete separation of the theca interna from the granulosa layer was performed, to demonstrate that A II affects separately the two individual cellular components of the follicular wall. We could show that theca is a source of estradiol whose production under human chorionic gonadotropin (hCG) stimulation was reduced by A II. At the same time, A II increased the in vitro hCG-stimulated secretion of testosterone by theca. In granulosa, A II decreased hCG-stimulated aromatization of androstenedione to estradiol but did not alter the release of hCG-stimulated progesterone production. These results suggest that A II could induce locally an increase in follicular fluid androgen/estrogen ratio and possibly participate in causing atresia. C. Féral, EP CNRS 009, Laboratoire de Biochimie, CHU Caen, F-14032 Caen Cedex, France

The circulating reninangiotensin system (RAS) participates in the regulation of blood pressure and electrolyte metabolism. Renin, a proteolytic enzyme, synthesized in the kidney from its biological precursor, prorenin, cleaves its substrate angiotensinogen in the blood to form the active octapeptide, angiotensin II (AII). All the RAS components are present in the reproductive system of mammals. During pregnancy, the level of prorenin increases in the plasma. The ovary is the source of this prorenin during early pregnancy and maternal decidua later on. During the menstrual cycle, the thecal of preovulatory follicles synthesize prorenin, renin and AII. Thecal renin synthesis is controlled by LH/hCG as demonstrated in vivo and in vitro in the rabbit. Ovarian renin seems to be identical to kidney renin. Prorenin appears to be the major secretory product rather than renin, which remains intracellular. AT2-type angiotensin II-receptors are expressed in the rat on follicular granulosa cells and could be down-regulated by FSH. The bovine thecal cells also express AT2-receptors, up-regulated by LH. These data are consistent with an autrocrine or paracrine role for ovarian RAS. It has been implicated in neovascularization of the follicle and regulation of steroidogenesis by increasing the androgen/estrogen ratio, an index of follicular atresia.

The origin of ovarian renin and its regulation by hCG were investigated in rabbit periovulatory follicles and cultured preovulatory follicular cells. Intracellular content of renin in thecal cells was 8-fold greater than of granulosa cells. In vivo, administration of hCG increased intracellular content of renin in thecal but not granulosa cells. Similar results were obtained for cultured follicular cells, from which renin was partly released into the medium. In vitro, hCG increased intracellular renin content of thecal but not granulosa cells, without obvious effect on release. Approximately 95% of ovarian renin was inactive, but could be activated by trypsin. Thecal renin was antagonized in vitro by renin antiserum, indicating a specific renin activity. Our study establishes in the rabbit the thecal cell origin of ovarian inactive renin and demonstrates hCG regulation of its synthesis.

In the Calyptraeidae, which are protandric hermaphrodite molluscs, the external male genital tract and the gonad develop synchronously. The penis appears in young animals but regresses at the time of sex inversion. Experiments carried out in Crepidula fornicata, using the organ culture technique, enabled us to prove that involution of the penis in vitro is not the result of an intrinsic cycle of this organ. Hormonal exposure which had occurred in vivo was sufficient to condition further development of the isolated penis in vitro. A pedal morphogenetic factor and a pleural regressive factor are responsible for the differentiation of the male genital tract. The programming depends upon a balance of these neuroendocrine factors in the animal that provided the explant. Notwithstanding its regression in vitro, the penis of Crepidula represents an organ unable to evolve by itself, inasmuch as its development is directly dependent on the neuroendocrine system.