Effect of Retinoids on Follicular Cells.

Abstract

It has been demonstrated that topical application of all-trans retinoic acid and other retinoids can alter the hair-growth cycle in the C3H mouse model. The anagen phase is prolonged and the telogen phase is shortened. This effect is similar to the effect of minoxidil on the hair-cycle dynamics in this animal model. The levels of cellular retinoic acid binding protein measured by radioreceptor assay in whole skin of C3H mice were higher during anagen and lower during telogen. Topical application of certain retinoids caused elevated levels of cellular retinoic acid-binding protein (cRABP) in the whole skin homogenates during both phases of the cycle. Of the retinoids tested, those most effective in altering the levels of cRABP in the skin of the mice were also capable of significantly altering the hair-cycle dynamics. There appeared to be a relationship between the ability of retinoid to increase cRABP, increase 3H-thymidine incorporation, and alter the dynamics of the hair cycle. Only cRABP-II is detectable in human cultured dermal fibroblasts and dermal papilla cells. Dermal fibroblasts showed higher amounts of cRABP-II as compared to dermal papilla cells. The difference in cRABP-II expression might explain a distinct response to RA by these two cell populations. Whether the difference in expression of cRABP-II might be of physiologic importance remains to be determined. Treatment of human dermal papilla cells in culture with retinoic acid does not appear to affect proliferation, at least at the doses tested.

Retinol Esterification by DGAT1 Is Essential for Retinoid Homeostasis in Murine Skin

“…In the absence of DGAT1, mice exhibited altered hair cycling, characterized by an increased propensity of follicles to be in anagen. These findings are consistent with a study in mice, in which topical retinoids applied to telogen hair follicles rapidly stimulated and prolonged anagen (40). Our results are also consistent with observations that retinoids exert diverse effects on hair, including promoting hair loss and, paradoxically, hair growth (40,41).…”

Regulation of human dermal papilla cell production of insulin-like growth factor binding protein-3 by retinoic acid, glucocorticoids, and insulin-like growth factor-1

“…Although the nature of the agent(s) which mediates these interactions is not presently known, several observations in the literature implicate the IGF signalling system (Hansson et al, 1988;Messenger, 1989;Little et al, 1993;Philpott et al, 1994). In the present studies, we show that IGFBP-3 is a predominant IGF binding protein secreted by DP cells and that its level is increased by retinoids and glucocorticoids, agents that regulate hair growth and/or time in anagen (Bazzano et al, 1993;Stenn et al, 1993;Berth-Jones and Hutchinson, 1995). Our results are consistent with a model that implicates IGFBP-3 as a control protein that could modulate the growth and formation of hair and/or hair follicle.…”

“…In ectocervical epithelial cells IGFBP-3 inhibits the mitogenic effects of IGF1, presumably by forming a complex with and preventing IGFl from interacting with the transmembrane type I IGFl receptor (i.e., lowering the concentration of free IGF in the extracellular environment) (Andreatta-van Leyen et al, 1994;Hembree et al, 1994). In DP cells, in contrast, IGFBP-3 does not appear to alter proliferation rate, since retinoids do not inhibit DP cell proliferation (Bazzano et al, 1993). This is not surprising, since DP cells are not believed to be highly proliferative.…”

The triacylglycerol synthesis enzyme DGAT1 also catalyzes the synthesis of diacylglycerols, waxes, and retinyl esters

“…The high levels of unesterified retinol in the livers of Dgat1 Ϫ/Ϫ mice also raise the possibility that alterations in retinoid metabolism may contribute to the phenotype of mice lacking DGAT1. Retinol is the precursor for retinoic acids (all-trans and its isomer 9-cis retinoic acids), which are ligands for the nuclear hormone receptors retinoic acid receptor and retinoid-X receptor (41)(42)(43), and retinoids affect sebaceous gland function (44,45), hair growth (46), and proliferation of mammary gland epithelial cells (47,48), all of which are part of phenotypic changes observed in Dgat1 Ϫ/Ϫ mice (17,22,23).…”