Paracrine Control of Gonadotrophs by Somatolactotrophs through TRH-induced Follistatin Production

ABSTRACT

There is increasing evidence for the existence of local regulation of hormone secretion among pituitary cells. Hormone-producing pituitary cells may communicate with each other and with folliculostellate cells. Activin is one of the regulators of follicle stimulating hormone (FSH) secretion and gene expression, whereas follistatin negatively regulates FSH production by binding to and bioneutralizing the effects of activin. In prolactin-secreting GH3 cells, hypothalamic thyrotropin-releasing hormone (TRH) has been known to stimulate prolactin synthesis and secretion. Follistatin is produced in GH3 cells and is up-regulated by TRH in an ERK dependent manner. Prolactin mRNA levels in GH3 cells are not affected by increasing the dose of exogenous follistatin, and TRH-induced prolactin expression is not modulated in the presence of follistatin. Follistatin produced in somatolactotroph GH3 cells does not affect prolactin production in these cells. In pituitary gonadotroph cell line, LβT2, activin increases FSHβ promoter activity and mRNA expression, and follistatin completely inhibits this activin-increased FSHβ gene expression. On the other hand, activin reduces the basal activity of prolactin transcription and follistatin prevents these effects. When GH3 cells and LβT2 cells are co-cultured, activin-induced FSHβ promoter activity is completely inhibited in the presence of follistatin. In addition, FSHβ mRNA is not detected in LβT2 cells, when co-cultured with GH3 cells. These observations using the model for somatolactotroph and gonadotroph suggest the possibility that somatolactotrophs and gonadotrophs interact with each other, and TRH might indirectly affect gonadotropin production though follistatin.

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