Kit Ligand and the Somatostatin Receptor Antagonist, BIM-23627, Stimulate in Vitro Resting Follicle Growth in the Neonatal Mouse Ovary

Abstract

In the mammalian ovary, kit ligand (KL), coded by a cAMP-stimulatable gene, is a protein that promotes initiation of follicle growth. The neuropeptide somatostatin (SST) is a small peptide that inhibits cAMP generation in many cell types. Consequently, SST receptor agonists might alter KL production and subsequent follicle growth. The present study was undertaken to look for the existence of a functional SST system in the mouse ovary, to test the effects of the SST receptor 2 (SSTR-2) antagonist BIM-23627 on in vitro folliculogenesis, and to compare them with those of KL, which was demonstrated to stimulate follicle growth in the neonatal rat ovary. Pairs of ovaries from 5-d-old mice were incubated in vitro during 15 d in the presence of either KL or BIM-23627. For every mouse, one ovary was cultured in culture medium (control), and the other ovary was cultured in the presence of either KL or BIM-23627. After 5, 10, and 15 d culture, the ovaries were histologically assessed for the content of primordial, primary, and secondary follicles. The SSTR-2 and -5, but not SST, were identified at the transcriptional and translational (mainly in granulosa cells) levels. Both KL and BIM-23627 triggered a reduction of the percentages of primordial follicles and an increase of the percentages of primary and secondary follicles when compared with control ovaries from the same animal. In conclusion, extraovarian SST, acting through its receptors 2 and 5 present on granulosa cells, may be involved in mouse folliculogenesis by reducing recruitment of resting follicles.