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Cyclic Changes in Follistatin Messenger Ribonucleic Acid and its Protein in the Rat Ovary During the Estrous Cycle^*

AKIRA NAKATANI, SHUNICHI SHIMASAKI, LOUIS V. DEPAOLO, GREGORY F. ERICKSON and NICHOLAS LING

Department of Molecular Endocrinology, Whittier Institute for Diabetes and Endocrinology La Jolla, California
Department of Reproductive Medicine, University of California San Diego, La Jolla, California 92093

Address all correspondence and requests for reprints to: Dr. Gregory F. Erickson, Department of Reproductive Medicine, University of California, San Diego, La Jolla, California 92093-0625.

Abstract

The purpose of this research was to characterize the localization of follistatin mRNA and protein in the adult rat ovary during the 4-day estrous cycle. Analysis of ovarian sections using in situ hybridization and immunohistochemistry demonstrated the presence of follistatin messenger RNA (mRNA) and its protein in granulosa and luteal cells; no follistatin (message or protein) was detected in any of the other ovarian cell types. An important observation was that the intensity of follistatin signals changed during granulosa differentiation and the estrous cycle. During folliculogenesis, the first detectable hybridization signal appeared in the granulosa cells of secondary follicles, but the signal was weak. However, when a preantral follicle reached the early tertiary stage (beginning antrum formation), the message signal was very strong, being expressed in all granulosa cells of all such follicles (300–400 µm in diameter). In atretic follicles, follistatin mRNA was localized to granulosa cells, but only during the early stages. The above hybridization pattern of follistatin mRNA in preantral and atretic follicles appeared constant throughout the estrous cycle. Interestingly, immuno-histochemistry studies showed that the follistatin protein was detected only in certain follicles, being restricted to those which were healthy. On the morning of estrus, the follistatin protein was localized to a subpopulation of early tertiary follicles, presumably the dominant follicles selected to ovulate in the next cycle. As the dominant preovulatory follicles matured through diestrus and proestrus, the follistatin mRNA and protein signals appeared more intense in the granulosa cells. After ovulation, the hybridization and immunohistochemical signals continued to be strong in the newly formed corpora lutea on estrus morning. After luteolysis on diestrus-I, neither the follistatin message nor the protein was detectable in the corpora lutea. In conclusion, these results suggest that the follistatin message is present in all the granulosa cells of every developing follicle throughout the estrous cycle, but the follistatin protein appears to be present in only the selected dominant follicles. Accordingly, the possibility that follistatin might be an important regulatory molecule for selection/atresia should be considered.

Footnotes

^* This work was supported by NICHD Program Project Grants HD-09690 and DK-18811, NICHD contract NO1-HD-0-2902, and NICHD Research Grant HD-24585.

Present address: Department of Pathology, Nagasaki University, School of Medicine, 12–4 Sakamoto-Machi, Nagasaki, 852, Japan.

Received January 30, 1991.

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