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This Article Full Text Full Text (PDF) All Versions of this Article: 77/1/18    most recent biolreprod.106.058230v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Spicer, L.J. Articles by Aad, P.Y. Search for Related Content PubMed PubMed Citation Articles by Spicer, L.J. Articles by Aad, P.Y. Agricola Articles by Spicer, L.J. Articles by Aad, P.Y.

Insulin-Like Growth Factor (IGF) 2 Stimulates Steroidogenesis and Mitosis of Bovine Granulosa Cells Through the IGF1 Receptor: Role of Follicle-Stimulating Hormone and IGF2 Receptor¹

Department of Animal Science, Oklahoma State University, Stillwater, Oklahoma 74078

ABSTRACT

Little is known regarding the role of insulin-like growth factor 2 (IGF2) and the regulation of the IGF2 receptor (IGF2R) during follicular development. Granulosa cells were collected from small (1–5 mm) and large (8–22 mm) bovine follicles and were treated with IGF2 for 1–2 days in serum-free medium, and steroid production, cell proliferation, specific ¹²⁵I-IGF2 binding, and gene expression were quantified. IGF2 increased both estradiol and progesterone production by granulosa cells, and cells from large follicles were more responsive to the effects of IGF2 than those from small follicles. Abundance of aromatase (CYP19A1) mRNA was stimulated by IGF2 and IGF1. The effective dose (ED₅₀) of IGF2 stimulating 50% of the maximal estradiol production was 63 ng/ml for small follicles and 12 ng/ml for large follicles, and these values were not affected by FSH. The ED₅₀ of IGF2 for progesterone production was 20 ng/ml for both small and large follicles. IGF2 also increased proliferation of granulosa cells by 2- to 3-fold, as determined by increased cell numbers and ³H-thymidine incorporation into DNA. Treatment with IGF1R antibodies reduced the stimulatory effect of IGF2 and IGF1 on estradiol production and cell proliferation. Specific receptors for ¹²⁵I-IGF2 existed in granulosa cells, and 2-day treatment with estradiol, FSH, or cortisol had no significant effect on specific ¹²⁵I-IGF2 binding. Also, FSH treatment of small- and large-follicle granulosa cells had no effect on IGF2R mRNA levels, whereas IGF1 decreased IGF2R mRNA and specific ¹²⁵I-IGF2 binding. Granulosa cell IGF2R mRNA abundance was 3-fold greater in small than in large follicles. These findings support the hypothesis that both IGF2 and its receptor may play a role in granulosa cell function during follicular development. In particular, increased free IGF1 in developing follicles may decrease synthesis of IGF2R, thereby allowing for more IGF2 to be bioavailable (free) for induction of steroidogenesis and mitogenesis via the IGF1R.

follicle, follicular development, granulosa cells, IGF2 receptor, insulin-like growth factor receptor, insulin-like growth factor 2

¹Supported by National Research Initiative Competitive Grant 2005-35203-15334 from the United States Department of Agriculture Cooperative State Research, Education, and Extension Service. Approved for publication by the director of the Oklahoma Agricultural Experimental Station, and supported in part under project H-2510.

Correspondence: ²Leon J. Spicer, 114 Animal Science Bldg., Department of Animal Science, Oklahoma State University, Stillwater, OK 74078. FAX: 405 744 7390; e-mail: leon.spicer{at}okstate.edu

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