Androgen-Dependent Beard Dermal Papilla Cells Secrete Autocrine Growth Factor(s) in Response to Testosterone Unlike Scalp Cells

Abstract

Androgens stimulate many hair follicles, e.g., beard, but may cause regression on the scalp; occipital areas are considered androgen independent. The mesenchyme-derived dermal papilla that regulates the hair follicle is considered the site of androgen action. Because hair size has been clearly related to dermal papilla size, one of the key functions androgens must regulate is the size of the dermal papilla. This implies that androgens stimulate dermal papilla cells to divide or to secrete autocrine mitogenic factors. As physiologic levels of androgens do not stimulate mitogenesis in cultured dermal papilla cells, this study was designed to determine whether dermal papilla cells cultured from human hair follicles with different responses to androgens in vivo, i.e., androgen-dependent beard and androgen-independent nonbalding scalp, produce soluble autocrine mitogenic factors and, if so, whether either cell type altered their secretion in response to testosterone in vitro. Conditioned medium was prepared by incubating individual primary lines of cells for 24 h with, and without, testosterone (10(-10)-10(-5) M). All conditioned media significantly increased [3H] thymidine incorporation by other dermal papilla cells; trypsin treatment significantly reduced the effect. Although both beard and scalp cell conditioned media had a similar stimulatory potential, beard cells incorporated approximately double the [3H]thymidine of scalp cells, in both types of media. Physiologic levels of testosterone increased mitogenic factor production by beard, but not scalp cells; only beard cells responded to these factor(s). Testosterone added after conditioning had no effect, indicating stimulation was not a synergistic effect of testosterone and conditioned medium. Thus, both beard and scalp cells release similar autocrine growth factor(s), but their response to these factor(s) is determined by their in vivo origin. Testosterone in vitro stimulates secretion of an autocrine growth factor(s) by beard, but not scalp cells, to which only beard cells are able to respond, reflecting the responses to androgens in vivo. These factors may be involved in the key increase of dermal papilla size necessary for androgen-induced changes in hair size.