Possible role of growth hormone, IGFs, and IGF-binding proteins in the regulation of ovarian function in large farm animals

The aim of the study and short review was to present evidence that growth h ormone (GH), locally produced insulin-like growth factors (IGFs), and IGF-b inding proteins (IGFBPs) may have an important role in the control of ovari an function. There is clear evidence for a distinct GH-receptor mRNA expres sion and protein production in follicles (oocytes and granulosa-cumulus cel ls) and corpus luteum (CL). In hypophysectomized ewes, GH and LH are necess ary for normal CL development. IGF-1 mRNA in the follicles is expressed in theca interstitial cells (TIC) and granulosa cells (GC) with already higher levels in the TIC before follicle selection. In contrast, IGF-2 is mainly expressed in the TIC. The IGFR-1 mRNA is expressed in both the TIC and GC, with increasing levels in GC during the final development of dominant folli cles. IGF-1 is a very potent stimulator of progesterone and oxytocin releas e in GC. IGFBP-1, -2, -3, -4, -5, and -6 have been isolated from follicular fluid or ovarian tissue. Studies indicate that IGFBP expression and produc tion in the developing follicle is dependent on both cell type and follicle size and is regulated by IGF-1 and gonadotropins. The highest expression o f IGF-1 and IGFR-1 mRNA was demonstrated during the early luteal phase. Dis tinct receptors for IGF-1 and IGF-2 were present in CL membrane preparation s at all stages investigated. Intense immunostaining for IGF-1 was observed mainly in bovine large and small luteal cells and in a limited number of e ndothelial cells. In contrast, IGF-2 protein was localized in perivascular fibroblast and pericytes of the capillaries. With the use of a microdialysi s system, we found that in vitro and in vivo IGF-1, IGF-2, and GH stimulate d the release of progesterone in cultures of luteal cells or intact tissues . In conclusion, there is clear evidence for a central role of the IGFs, IG FBPs, and GH in follicular development and CL function. (C) 1999 Elsevier S cience Inc. All rights reserved.