Changes in expression of epidermal growth factor receptors by anterior pituitary cells during the estrous cycle: cyclic expression by gonadotropes.

Epidermal growth factor (EGF) stimulates gonadotropin secretion, suggesting that it may regulate gonadotrope functions. These responses may be modulated by changes in expression of EGF receptors (EGFR), especially during the estrous cycle. To test this hypothesis, EGFR and pituitary hormones were detected by dual immunocytochemistry. Pituitary cells from metestrous rats contained 41 +/- 4% cells labeled for EGFR. This peak was followed by a decline to 17.6 +/- 2% of cells from proestrous rats. The percentages of metestrous pituitary cells with EGFR and each hormone were: PRL, 11.8 +/- 1; ACTH, 9.9 +/- 1.8%; GH, 8.2 +/- 0.6%; TSH, 6.3 +/- 0.8%; FSH, 4 +/- 0.6%; and LH, 2.6 +/- 0.6%. The relatively low percentages of gonadotropes may have reflected the low expression of LH or FSH antigens during metestrus. Dual labeling for EGFR and LHbeta or FSHbeta messenger RNAs (mRNAs) showed a significant increase in the percentages of pituitary cells with LHbeta mRNA and EGFR (to 5.7% of pituitary cells), but there were no increases in the EGF target cells bearing FSHbeta mRNA. When gonadotropin antigens were detected in EGF target cells during other stages of the cycle, there was an increase to reach a peak of 6.6-7% of pituitary cells by the morning of proestrus (or 40-50% of gonadotropes). To summarize, EGFR are seen in few gonadotropes during the metestrous peak, although more LH cells (but not FSH cells) can be identified by their content of LHbeta mRNA. This suggests that EGFR is expressed initially in monohormonal LH gonadotropes. The peak expression of EGFR by gonadotropes during diestrus and proestrus suggests that EGF may be involved in the development of the gonadotropes as they approach surge secretory activity. It also may help stimulate the transcription of new gonadotropin beta-subunit mRNA seen late in proestrus, early in estrus.