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Hormones
Their relationship to skin is essential to understanding esthetics

By Benjamin Fuchs

Originally published in Skin Deep, September/October 2009. Copyright 2009. Associated Skin Care Professionals. All right reserved.

The human body is a complex, intricate, yet remarkably integrated biological machine composed of as many as 100 trillion cells. It accomplishes its awe-inspiring coherence through the actions of countless chemical reactions occurring on a nanosecond basis. All of this complexity and integrity requires the activity of messenger molecules called hormones.

Hormones have a vital role to play, via their mediating activity, in thousands of biochemical activities in the human body. No organ system demonstrates the important role hormones play in human health more dramatically than skin, due to its dynamic nature. In fact, not only is skin a target structure for various hormonal molecules, but it can actually be considered a peripheral endocrine hormone organ in its own right. Given the important role these substances play in skin health and chemistry, it is critical that skin care professionals have a basic grasp on the nature of hormone chemistry.


Endocrine System
In order to understand the role hormonal substances play in biological and skin health, some background on the science of hormones, known as endocrinology, is necessary. The endocrine system involves structures called glands that secrete their chemicals (hormones) directly into the bloodstream. (To be accurate, there are other hormonal substances, including autocrine, exocrine, and paracrine hormones, that do not use the bloodstream. We will not be discussing these.) From the bloodstream, individual hormones travel to so-called target cells where they have their effects.

There are two major types of hormonal molecules--lipid-like molecules known as steroids and amino acid-based (protein-like) chemicals known as peptides. Although some biochemists classify essential fatty acid derivatives like prostaglandins, and vitamins like the retinoids (Vitamin A) and calciferols (Vitamin D), as hormonal, we will limit our focus to the two major hormone classifications, which have significant roles to play in skin health.

When most people think of hormones, the ones that immediately come to mind are the steroid hormones. Perhaps this is because of the dramatic decline in their activity that can occur with aging or ill health. Or it may be because of the many skin care (and healthcare) issues that are associated with their decrease. Steroid hormone synthesis occurs in the skin.

Steroid hormones are manufactured primarily in the gonads (ovaries and testes) and the adrenal glands, although many other cell types are capable of producing these substances. Regardless of where they are produced, all steroid hormones are derived from cholesterol. Given their name from their common structural (steroid) base, there are five major classes of steroid hormones, each with particular roles to play in skin health.


Steroid Hormones
Estrogens. These are named for their role in the estrous (menstrual) cycle, and comprise the first and possibly the most significant group of steroid hormones for the skin. Documentation on the benefits of estrogen is voluminous and well-described.

Estrogen is involved in helping maintain skin health in several ways. Skin cells and fibroblasts contain estrogen and estrogen receptors. That may account for this important hormone's ability to help prevent decreases in collagen and elastic fibers, helping improve wrinkles, and supporting skin thickness. Topical estrogen creams have been shown to have many beneficial effects on aging skin. This hormone family helps skin hydration by increasing mucopolysachharides and hyaluronic acid levels and by increasing epidermal cell division. It may also be involved in helping improve stratum corneum barrier function and sebaceous flow (although some sources indicate estrogen may reduce the size of sebaceous glands). Estrogen has also been shown to improve wound healing. Elevated estrogen levels, however, have been associated with melasma--the mask of pregnancy--or in the hyperpigmentation associated with oral contraceptives.

Progestogens. These are named for their role in promoting pregnancy and function as precursors to other steroid hormones. They are intermediate products in the biosynthetic pathway of estrogens. The most prominent progestogen, progesterone, is secreted by the corpus luteum, thus its levels tend to rise in women after ovulation. Progesterone is involved in far more than the female reproductive system. Progesterone levels have an effect on kidneys, male prostate and sperm health, the central nervous system, and the immune and respiratory systems. Although there are not a lot of studies documenting the role of this hormone on skin, a double-blind study published in a 2005 British Journal of Dermatology article showed a strong correlation--without side effects--between progesterone and a reduction in wrinkles. It has also been shown that progesterone can decrease collagenase, the enzyme responsible for the degradation of collagen.

Androgens. This group of steroid hormones is represented by testosterone and its many derivatives. Androgens are anabolic (growth-inducing) and play an important role in the development of skin cells and other important cutaneous structures. Skin has been shown to possess all the necessary biochemicals required for their synthesis, and skin issues such as acne, hirsutism, and seborrhea can be related to pathologies in the production of skin androgens. Keratinocytes contain androgen receptor sites and elevated androgen levels have been associated with keratinocytic hyperproliferation and the subsequent formation of acne comedones. Experimental removal of androgen-producing glands in castration resulted in markedly reduced skin thickness and collagen content. Androgen stimulation is associated with sebaceous gland growth and differentiation, epidermal barrier stability, and wound healing.

Glucocorticoids. The primary activities of glucocorticoids, the fourth important class of steroid hormones, are derived from cortisol. Glucocorticoids have a long history of effectiveness as therapeutic agents for various disorders of the skin. Glucocorticoid metabolite hydrocortisone's ability to reduce immune and inflammatory response has made it the topical drug of choice for treating numerous skin diseases, including eczema uticaria and psoriasis. However, internally produced cortisol can actually be the cause of some skin problems. For example, elevated cortisol levels may impair wound healing and barrier repair. Glucocorticoids, in general, may also have a negative effect on hyaluronate accumulation via suppression of fibroblastic activity. And glucocorticoids may have an inhibitory effect on the production of collagens. This may have therapeutic benefit in the treatment of keloids. Finally, depletion of cortisol, which can occur in Addison's disease or adrenal fatigue issues, may result in pigment disorders such as post-inflammatory hyperpigmentation, melasma, or both. Replacement of cortisol has been shown to slowly reverse excessive skin pigmentation.

Mineralcorticoids. These substances, exemplified by the hormone aldosterone, exert their most important effects on salt and water balance. It has been noted that human skin is a target organ for mineralcorticoids. The presence of a sodium-retaining factor in the skin that may be dependent on mineralcorticoids may account for swelling that can appear in the skin and under the eyes. Elevated aldosterone levels are associated with adrenal stimulation and this may at least partially account for skin and undereye puffiness associated with physiological stress. Mineralcorticoids may also be involved in the production of skin proteins. In fact, a recent patent application makes a claim for aldosterone-induced elastic fiber production in skin tissue.


Peptide Hormones
The second major category of hormones is peptides, which can be further subdivided into the large-chain peptide (LCP) hormones and short-chain peptide (SCP) hormones. Peptide hormones, composed of strings of amino acids, are responsible for signaling or modulating the majority of biochemical reactions in the body. In the skin, peptide hormones have a role to play in almost every cutaneous reaction, from wound healing, to antiaging, to neural reactions that can manifest as sensitivities and pain.

Insulin. One of the most important of the peptide hormones, and arguably the most important hormone in the body, is insulin. Although commonly associated with sugar metabolism, insulin is more accurately associated with growth. Insulin (and its marker insulin-like growth factor) has been shown to stimulate collagen and proteoglycans synthesis. Elevated insulin levels have been associated with hypersebaceous activity, hyperproliferation of keratinocytes, and formations of comedones.

Thyroxin. This is the main hormone secreted from the thyroid gland, another peptide hormone with important effects on the skin. Epidermal keratinocytes are able to convert thyroxine to its active form and both thyroxine and epidermal growth factor have similar results on stimulating epidermal maturation. Removal of the thyroid is associated with decreases in sebum production. This can be reversed with the administration of thyroid hormone. The skin can actually be used in the preliminary diagnosis of thyroid disorders. For example, epidermal thickening is associated with hyperthyroidism, while skin dryness and excessive bruising may be associated with hypothyroidism. Elevated levels of hyaluronic acid demonstrated in patients with hypothyroidism may account for the characteristic edema associated with this pathology.

SCP hormones are responsible for the most important advance in skin care technology since the introduction of topical retinoids in the late 1970s. These small, biologically active molecules were first described more than 40 years ago. Since that time, hundreds of these substances have been discovered in various tissues and organs, including the skin. Like larger hormonal chemicals, SCPs function as messenger molecules that are released in one part of the body and exert their effects at another part. Like other endocrine hormones, SCPs are mostly transported through blood (or lymph). Their activity is usually short-lived and it is important that they are renewed regularly to maintain tissue health. This makes these molecules especially important for topical skin care, and indeed SCPs have found an important home in premium, therapeutic skin care products.

Growth Factors. Among the most significant peptides with skin relevance are the growth factors. Biochemicals like epidermal growth factor (EGF), keratinocytic growth factor (KGF), and fibroblastic growth factor (FGF) have obvious roles to play in skin health. The levels of these important molecules are tightly
regulated and linked to various factors, like diet, secretion of other hormones, and wounding. Even production of neurotransmitters in the brain, related to changes in mood, has been shown to be associated with levels of these substances.

Recently, it has been shown that keratinocytes are able to produce and secrete peptides that may be involved in the manifestation of sensitive skin. And, it has been shown that skin cell production of a peptide called Substance P is associated with the exacerbation of dermatitis, itch, nerve pain, and vasodilation. This has led to attempts to produce materials that can have an antagonistic effect on these materials to improve skin health.

Studies in wound healing and aging have led researchers to isolate skin peptide hormones that can have stimulatory effects on the synthesis of tissue-building substances. Some have an ability to improve the production of collagen or decrease its breakdown. Others are associated with improving the manufacture of glucoseaminoglycans. Still others have shown an ability to up-regulate the production of growth factors and down-regulate the production of fiber-degrading enzymes. These substances may improve the appearance of some of the signs of aging including dryness, photo-damage, skin thinning, and wrinkles. As one might expect, many of these molecules have found their way into topical skin care preparations.


Billions of Skin Cells
This basic overview was designed to demonstrate the critical role of hormonal messenger molecules in the coordination of the numerous chemical reactions relevant to skin health. The miracle of coordination and cohesiveness accomplished by the trillions of cells in the human body and the billions of cells in human skin is dependent on the action of these substances. The skin's flexible and dynamic nature makes it especially dependent on the function of these important signaling molecules. SD

Benjamin Fuchs, RPh, is a nutritional pharmacist, cosmetic chemist, and formulator for Sanítas Skincare. He has been formulating custom skin care products for more than 20 years. Contact him through www.sanitas-skincare.com.




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