Acne-----HPA axis-----and CRH

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Physiology

Corticotropin-releasing hormone: An autocrine hormone that promotes lipogenesis

in human sebocytes

Christos C. Zouboulis*,, Holger Seltmann*, Naoki Hiroi,§, WenChieh Chen¶, Maggie

Young§, Marina Oeff*, Werner A. Scherbaum, Constantin E. Orfanos*, M.

McCann, and Stefan R. Bornstein,§

* Department of Dermatology, University Medical Center lin, The

Free University of Berlin, 14195 Berlin, Germany; Department of Endocrinology,

University Medical Center, Heinrich Heine University of Duesseldorf, 40225

Duesseldorf, Germany; § Pediatric and Reproductive Endocrinology Branch,

National Institute of Child Health and Development, National Institutes of

Health, Bethesda, MD 20892-1583; ¶ Department of Dermatology, College of

Medicine, National Cheng Kung University, 704 Tainan, Taiwan; and Pennington

Biomedical Research Center, Baton Rouge, LA 70808-4124

Contributed by M. McCann, March 27, 2002

Sebaceous glands may be involved in a pathway conceptually similar to that of

the hypothalamic-pituitary-adrenal (HPA) axis. Such a pathway has been described

and may occur in human skin and lately in the sebaceous glands because they

express neuropeptide receptors. Corticotropin-releasing hormone (CRH) is the

most proximal element of the HPA axis, and it acts as central coordinator for

neuroendocrine and behavioral responses to stress. To further examine the

probability of an HPA equivalent pathway, we investigated the expression of CRH,

CRH-binding protein (CRH-BP), and CRH receptors (CRH-R) in SZ95 sebocytes in

vitro and their regulation by CRH and several other hormones. CRH, CRH-BP,

CRH-R1, and CRH-R2 were detectable in SZ95 sebocytes at the mRNA and protein

levels: CRH-R1 was the predominant type (CRH-R1/CRH-R2 = 2). CRH was

biologically active on human sebocytes: it induced biphasic increase in

synthesis of sebaceous lipids with a maximum stimulation at 107 M and

up-regulated mRNA levels of 3- hydroxysteroid dehydrogenase/5-4 isomerase,

although it did not affect cell viability, cell proliferation, or IL-1-induced

IL-8 release. CRH, dehydroepiandrosterone, and 17-estradiol did not modulate

CRH-R expression, whereas testosterone at 107 M down-regulated CRH-R1 and CRH-R2

mRNA expression at 6 to 24 h, and growth hormone (GH) switched CRH-R1 mRNA

expression to CRH-R2 at 24 h. Based on these findings, CRH may be an autocrine

hormone for human sebocytes that exerts homeostatic lipogenic activity, whereas

testosterone and growth hormone induce CRH negative feedback. The findings

implicate CRH in the clinical development of acne, seborrhea, androgenetic

alopecia, skin aging, xerosis, and other skin disorders associated with

alterations in lipid formation of sebaceous origin.