Activin and Inhibin Effects

Activin and inhibin control of gonadotrope function.

Studies in G.V. Childs' lab, The University of Arkansas for Medical Sciences

Activin and Inhibin are polypeptides that stimulate and inhibit FSH secretion, respectively. Their subunits were first discovered in the gonads. However, they are also found in gonadotropes themselves. This suggests self- or autocrine regulatory mechanisms. We would like to know if a particular subset of gonadotropes produces these polypeptides. We would also like to learn more about the interactions between activin, inhibin and their target cells.

Activin increases numbers of LH or FSH cells.

We have discovered that if you pretreat pituitary cells from rats on the day before ovulation with 10-50 ng/ml activin, there is an increase in the percentages of gonadotropes that bear LH or FSH antigens (detected by immunocytochemistry ). Thus, activin clearly helps to augment the gonadotrope population. These data are shown in the following figure

Note that inhibin has no effect on the percentages of LH or FSH cells. However, if inhibin is given on the day of ovulation, it decreases the percentage of FSH cells by 50-60% (data not shown). Future studies are needed to learn if activin and inhibin have target cells among the subsets of gonadotropes. For example, we know that medium-sized gonadotropes are mainly responsible for the augmentation in the population just before ovulation. Perhaps these cells are stimulated by activin. It would also be of interest to learn how the medium-sized cells respond to both activin and estradiol.

for more information, please see the following papers:

Childs GV, Miller, B, and Miller W. 1997 Differential effects of inhibin on gonadotropin stores and gonadotropin releasing hormone binding to pituitary cells from cycling female rats. Endocrinology 138: 1577-1584.

Childs GV and Unabia G 1997 Cytochemical studies of the effects of activin on gonadotropin releasing hormone (GnRH) binding by pituitary gonadotropes and growth hormone cells. J Histochem Cytochem 45: 1603-1610

GnRH binding is modulated by steroids, activin, and inhibin.

We have studied sites of GnRH binding with affinity cytochemistry since 1983. GnRH binding can be detected on cells that store LH or FSH antigens with the use of dual labeling techniques. Studies by a former graduate student, Dr. Robert Tibolt, showed that GnRH binding can be decreased following pretreatment with testosterone. Dr. Jon Lloyd showed that in females, estrogen treatment 1-2 days before ovulation will increase the percentages of cells that bind GnRH.

Recently we have discovered that activin treatment the day before ovulation will increase the percentages of cells that bind GnRH. This increase occurs in the gonadotrope population. Inhibin decreases the percentages of GnRH-receptive pituitary cells when given either the day before ovulation, or the day of ovulation. The following figure on the illustrates these data.

for more information, please see the following papers:

Some early publications describing modulation of GnRH binding.

Tibolt, R.E. and Childs, G.V. Cytochemical and cytophysiological studies of GnRH target cells in the male rat pituitary: Differential effects of androgens and corticosterone on GnRH binding and gonadotropin release. Endocrinology 117(1):396-404, 1985.

Lloyd, J.M. and Childs, G.V. Changes in the number of GnRH-receptive cells during the rat estrous cycle: biphasic effects of estradiol. Neuroendocrinology 48:138-146, 1988

Ghosh, BR, J.C., Wu, G.V. Childs, and W.L. Miller, Inhibin and Estradiol Alter Gonadotropes Differentially in Ovine Pituitary Cultures: Changing Gonadotrope numbers and Calcium Responses to Gonadotropin-Releasing Hormone, Endocrinology, 137: 5144-5154, 1996.

Protocols and related web pages:

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