Decrease of Insulin Growth Factor-1 as a Novel Mechanism for Anti-Androgen Effect of Isotretinoin and Its Reported Association With Depression in Some Cases

July 2011 | Volume 10 | Issue 7 | Original Article | 793 | Copyright © 2011

Abstract

Isotretinoin and its desirable effects have received tremendous attention in recent years by scientists. This article reviews the evidence that decrease of insulin growth factor-1 is implicated as a novel mechanism of anti androgenic effect and its reported association with depression in some cases.

J Drugs Dermatol. 2011;10(7):793-794.

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INTRODUCTION

Isotretinoin (13-cis retinoic acid) has been widely used for the treatment of severe cystic or recalcitrant acne vulgaris since 1982.1 Isotretinoin is an effective medication, but a broad range of side effects for it has been described in the medical literature. The exact mechanisms underlying the desirable effects as well as the untoward effects of this commonly used medication have not yet been unraveled. Herein, some light is shed on this unexplored subject, along with a suggestion that decrement of IGF-1 could contribute to the anti-acne effect of isotretinoin through antagonizing androgen effects as well. Commentary is also extended to explain the reported triggering of depression by isotretinoin in some patients taking this drug.

Recently, Karadag et al. reported an interesting relationship between isotretinoin use and decrease of the level of insulin growth factor-1 (IGF-I) after three months of treatment.1

It has been suggested that insulin-like growth factor type I receptor (IGF-IR) signaling interacts with androgen receptor activation.2 Notably, androgen significantly stimulates the proliferation of outer root sheath cells that are co-cultured with beard dermal papilla cells without cell contact. The expression of insulin-like growth factor I (IGF-I) mRNA in beard dermal papilla cells was stimulated by androgen and antagonized by cyproterone acetate. Neutralizing antibody against IGF-I antagonized the stimulatory effect of androgen on the growth of outer root sheath cell co-cultured with beard dermal papilla cells. These findings suggest that androgens exert their biologic effects at least partly through stimulation of IGF-I production.3 More pertinent to acne is the finding that increased IGF-1 levels in response to androgen can trigger acne in adult men and especially women.4,5 In other words, in patients with clinical acne, the effects of androgens on increased acne lesion counts were dependent on the influence of IGF-1.4 Interestingly, IGF-1 levels are also known to be the highest during puberty, which is when sebum production begins and coincides with the occurrence of acne.4 Decrement of IGF-1 expression by isotretinoin, as shown by Karadag et al., can therefore explain the anti-acne effect of this agent through decreasing IGF-1 levels.1

Growth factors in the brain are important to depression and its treatment. It has been shown that mice that received chronic IGF-I treatment showed antidepressant-induced behavior.6 Decrement of IGF-1 expression by isotretinoin can therefore explain triggering of depression in some cases taking this medication.

The objective of this study was to assess common dermato-

In summary, we propose that decrement of IGF-1 may offer a novel mechanism for anti-androgen7 and anti-acne8 effects of isotretinoin and also its reported association with depression.9

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