Interaction of growth hormone and insulin-like growth factor-I in the control of steroidogenesis by cultured porcine granulosa cells

• Main Author: Xu, Yongping
• Other Authors: Thacker, Philip A.
• Format: Others
• Language: en
• Published: University of Saskatchewan 1996
• Online Access: http://library.usask.ca/theses/available/etd-10202004-235736

In order to better understand the factors controlling or modulating ovarian function, and in an attempt to develop a way to increase ovulation rate in gilts, the effects of metabolic hormones such as growth hormone (GH), insulin or prolactin and growth factors such as insulin-like growth factor I or II (IGF-I or IGF-II) on steroidogenesis in cultured porcine granulosa cells were investigated with emphasis on the interaction between GH and IGFs. Experiment one was conducted to examine the influence of metabolic hormones and growth factors on progesterone and estradiol secretion by porcine granulosa cells in culture, and to determine the possible site(s) of action of these agents on steroidogenesis. Both IGF-I and IGF-II increased (P $<$ 0.01) basal progesterone and estradiol secretion and enhanced the FK-and dbcAMP-induced stimulation of progesterone and estradiol secretion (P $<$ 0.01). Insulin, at 100 ng/ml, had a modest but significant positive effect on both FK- and dbcAMP stimulated steroidogenic responses. In contrast, GH inhibited basal, FK- and dbcAMP-induced progesterone and estradiol production. In experiment two, the interaction of GH and IGF-I in the acquisition of progesterone biosynthetic capacity was examined. Basal progesterone production was not affected (P $>$ 0.05) by GH treatment. However, concurrent treatment with GH produced a 4.1 fold increase (539 vs. 2214 ng/culture) in the IGF-I-stimulated accumulation of progesterone. In experiment three, the synergism of GH and IGF-I in the production of estradiol was examined in cultured porcine granulosa cells. The data provide what is believed to be the first demonstration of a synergistic interaction between GH and IGF-I in the induction of aromatase activity. The present experiment indicates that GH is capable of synergizing with IGF-I in the induction of estrogen production, an effect unaccountable by enhancement of protein synthesis. Experiment four demonstrated that swine granulosa cells are highly responsive to human recombinant IGF-II under serum-free conditions in vitro. Indeed, IGF-II was just narrowly lower in potency than IGF-I in stimulating progesterone production as shown previously (experiment one). Moreover, co-administration of GH in the culture medium increased IGF-II induced progesterone production. Porcine GH by itself did not have any effect on progesterone production and its amplification of progesterone accumulation can only be observed in the presence of IGF-II. In contrast, although the receptors for prolactin and GH belong to a similar family of single membrane-spanning cytokine/hematopoietin receptors and both prolactin and growth hormone utilize JAK2 as the signaling molecules, prolactin, at a dose of 600 ng/ml, had no amplifying effect on IGF-I induced progesterone accumulation. (Abstract shortened by UMI.)