It is well known that estrogen and testosterone play vital roles in the development of secondary sexual characteristics and are important for reproduction. There are also several ongoing investigations on the effects of these sex hormones in cardiovascular disease, neurodegenerative disease, mood, and cancer formation, as well as into their roles in adipogenesis and osteogenesis in women and men. With so many tissues expressing estrogen and androgen receptors, it is not surprising to find that several organ systems experience dramatic changes as sex hormone levels decline with advancing age. The first studies of sex hormone receptors in human skin and skin appendages began in the mid-1970s and examined estrogen receptors in breast cancer tissue,1 and testosterone receptors in human hair follicles.2 Since that time several studies have examined the roles of sex hormones in a variety of dermatologic and other disease states. While it has long been known that the skin has sex hormone receptors, the recent discovery of a second estrogen receptor (ER-β) has led to much interest in and new insights into the effects of sex hormones on various tissues including the skin. The aim of this chapter is to review the actions of sex hormones on the skin, specifically estrogen and testosterone, and to examine the roles of these hormones in skin aging.
SYNTHESIS OF SEX HORMONES AND THEIR DECLINE DURING AGING
Sex hormones are mainly synthesized in the gonads and the adrenal glands of humans. During puberty, both the male and female gonads begin to secrete testosterone. The prostate, a male secondary sex organ, can convert testosterone into the more potent dihydrotestosterone (DHT), which has an affinity 5 times as strong for the androgen receptor. During the female reproductive years, most of the testosterone produced by the ovaries is converted into estradiol (17β-estradiol), the physiologically active and most abundant estrogen during this time period. The other two types of physiologic estrogens are estrone and estriol. Estrone is the predominant estrogen after menopause, and estriol is synthesized by the placenta during pregnancy (Table 5-1). In the adrenal gland, the precursor to both estrogens and androgens is dehydroepiandrosterone (DHEA), a derivative of cholesterol. DHEA is converted into androstenedione in the adrenal gland. Both androstenedione and DHEA, which by themselves have weak androgenic activity, can enter the systemic circulation and be converted into testosterone or estrogen by peripheral target cells. The enzyme responsible for this conversion is aromatase. Both men and women have the ability to convert testosterone into estradiol via this enzyme. Besides the gonads, other tissues containing aromatase, and hence the ability to make estradiol or testosterone from DHEA, are bone, brain, vascular tissue, fetal liver, placenta, adipose tissue, and the skin3,4 (Table 5-2).
TABLE 5-1Types of Estrogen, Their Origin, and When Each Type Prevails