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-
