Marty E. Sawaya's research while affiliated with Pennsylvania State University and other places

Publications (40)

Chapter
Circulating androgens can profoundly influence target cutaneous structures such as the pilosebaceous unit (hair follicle and sebaceous gland), and play a central role in the pathogenesis of cutaneous disorders of hyperandrogenism (CHA) which include androgenetic alopecia (AGA), acne vulgaris, and hirsutism. Therapeutically, two main categories of d...
Article
Inflammasomes that activate caspase-1 govern the innate immune inflammatory response. Whether hair loss associated with androgenetic alopecia (AGA) involves caspase-1 activation is not known. Immunohistochemical staining for caspase-1 was performed on scalp tissue sections, and protein lysates were analyzed from individuals with AGA (no treatment),...
Article
CD44 is a widely distributed cell surface protein thought to be involved in multiple steps of normal immune cell function, including T-cell activation, and in cellular adhesion where it mediates cell attachment to hyaluronate. In normal skin, CD44 is found by immunohistochemical means to be primarily in eccrine coil cells. In this study, we have lo...
Article
Recently, the search for new and effective agents for the treatment of alopecia has become significantly more intense. The increase in hair biology research worldwide seen in both academic institutions and pharmaceutical companies stems from the desire to profit from the marketing of drugs that have been termed cosmeceuticals. Millions of men and w...
Article
Excessive sebum production is a central aspect of the pathophysiology of acne vulgaris. Sebaceous gland function is under androgen control and it is hypothesized that dihydrotestosterone is formed by the action of 5 alpha-reductase. Type I is the controlling isoenzyme. This study describes a 3-month, multicenter, randomized, placebo-controlled clin...
Article
This article contains a brief review of hair follicle biology, followed by a presentation of the workup of elderly patients who present with hair loss or hirsutism. Common hair disorders, such as graying, telogen effluvium, androgenic alopecia, senescent alopecia, alopecia arcuata, hirsutism, and hypertrichosis, are discussed.
Article
Background A number of studies have provided evidence that apoptosis is a central element in the regulation of hair follicle regression. In androgenetic alopecia (AGA), the exact location and control of key players in the apoptotic pathways remains obscure. Objective In the present study, we used a panel of antibodies and investigated the spatial...
Article
A number of studies have provided evidence that apoptosis is a central element in the regulation of hair follicle regression. In androgenetic alopecia (AGA), the exact location and control of key players in the apoptotic pathways remains obscure. In the present study, we used a panel of antibodies and investigated the spatial and cellular pattern o...
Article
Alopecia areata (AA) patients show a variable response in hair regrowth with glucocorticoid (GC) steroid treatment. The biochemical mechanisms by which GCs stimulate hair growth in patients with AA is unknown, yet clinicians commonly use topical, intralesional, and even oral GC steroid therapy to treat AA. In this study, scalp biopsy specimens were...
Article
Finasteride has been shown to be an effective treatment for men with androgenetic alopecia (AGA) as it restores hair growth to miniaturized hair follicles on the top of the scalp [1]. Caspases are regulators of programmed cell death, and very likely some specific caspases may function as mediators of the hair growth cycle. It is unclear whether fin...
Article
Hirsutism, the presence of terminal (coarse) hairs in females in a male-like pattern, affects between 5% and 10% of women. Of the sex steroids, androgens are the most important in determining the type and distribution of hairs over the human body. Under the influence of androgens hair follicles that are producing vellus-type hairs can be stimulated...
Article
Although there are new FDA-approved drug therapies to treat hair loss, there are many unapproved agents with claims of effectively treating hair loss. A variety of new over-the-counter agents are available for consumers to use; however, it is difficult to assess how these agents work, costs of these agents, and efficacy. This article covers the new...
Article
Recent approval in the United States of two new products, Propecia (Merck Co, Rahway, NJ) and Rogaine Extra Strength 5% (Pharmacia & UpJohn Co, Kalamazoo, MI), indicated in men to promote scalp hair growth, have added a new dimension to treatment options offered by physicians in treating androgenetic alopecia (AGA). The search for new and effective...
Article
The androgen receptor (AR) is a structurally conserved member of the nuclear receptor superfamily. The amino-terminal domain is required for transcriptional activation and contains a region of polyglutamine encoded by CAG trinucleotide repeats. In humans, the number of CAG repeats is polymorphic. Expansion of CAG repeats in the AR has clinical impl...
Article
In this study, 12 women and 12 men, ages 18-33 y, with androgenetic alopecia were selected for biopsies from frontal and occipital scalp sites. The androgen receptor, type I and II 5alpha-reductase, cytochrome P-450-aromatase enzyme were measured and analyzed in hair follicles from these scalp biopsies. Findings revealed that both women and men hav...
Article
It is now known that there are major differences in the systemic and cellular mechanisms that mediate hair loss in women versus men. The severity or degree of hair loss in women with androgenetic alopecia is usually much less than in men. It is usually assumed that the hormonal basis for androgenetic alopecia in women is the same as in men; that is...
Article
CD44 is a widely distributed cell surface protein thought to be involved in multiple steps of normal immune cell function, including T-cell activation, and in cellular adhesion where it mediates cell attachment to hyaluronate. In normal skin, CD44 is found by immunohistochemical means to be primarily in eccrine coil cells. In this study, we have lo...
Article
This article is a useful guide for treating androgen-related skin disorders such as androgenetic alopecia, acne, and hirsutism. All available antiandrogens are discussed, as well as treatment doses, efficacy, and mode of action.
Article
Human hair follicles (HF) and sebaceous glands (SG) were assessed for the presence and distribution of the cytochrome P-450-aromatase (AR) and 3B-hydroxysteroid dehydrogenase (3B-HSD) enzymes. Immunohistochemical methods were used to examine both enzymes in male and female human skin specimens at various ages and different body sites. AR was found...
Article
Human sebaceous glands (SG) and hair follicles (HF) are target structures in the skin for androgen action. They contain steroid enzymes, capable of transforming weak androgens into the target-tissue-active androgens testosterone (T) and dihydrotestosterone (DHT), which bind to the androgen receptor (AR) to regulate cellular transcription. The AR fr...
Article
ImuVert, a biologic response modifier, and interleukin 1 (IL 1) have been shown to protect the young rat from alopecia induced by cytarabine (ARA-C). In the present study the inhibition by ARA-C of DNA synthesis in hair follicles (HFs) and the protective effect of ImuVert and IL 1 were investigated in vivo and in vitro. Both ImuVert and IL 1 were e...
Article
Human hair follicles contain several steroid enzymes capable of transforming weak androgens, such as dehydroepiandrosterone, into more potent target tissue androgens, such as testosterone and dihydrotestosterone. Kinetic constants have been evaluated for the 3-alpha, 3-beta, and 17-beta hydroxysteroid dehydrogenase enzymes, 5a-reductase, and the ar...
Article
Sebaceous glands were isolated by manual dissection under a microscope from surgical specimens of scalp skin with male pattern baldness and skin specimens of hairy and bald scalp obtained at autopsy. The 800 X g pellet (nuclear fraction) and the 164,000 X g supernatant fraction (cytosol) of homogenates of the sebaceous glands were used for measurem...
Article
Sebaceous glands were isolated by manual dissection using a stereomicroscope from skin specimens of bald scalp of men with male-pattern baldness undergoing hair transplant or scalp reduction surgery and also from specimens taken from hairy and bald areas of scalp at autopsy of adult male victims of accidental death within 3 h post mortem. Homogenat...
Article
Sebaceous glands were isolated by manual dissection using a stereomicroscope from skin specimens of bald scalp of men with male-pattern baldness undergoing hair transplant or scalp reduction surgery and also from specimens taken from hairy and bald areas of scalp at autopsy of adult male victims of accidental death within 3 h post mortem. Homogenat...
Article
We have measured oestrogen and progesterone binding in specimens of histopathologically confirmed lentigo maligna (LM) lesions excised from five elderly white men, using a dextran-coated charcoal method. Oestrogen binding was observed in four of the five specimens, and progesterone binding in all five. Marginal normal skin showed only non-specific...
Article
After intracardial injection of [1,2-3H]dehydroepiandrosterone ([3H]DHA) into female rats, [3H]DHA was found to accumulate and was metabolized in the preputial gland, but not in the diaphragm. The identified metabolites of [3H]DHA in the preputial gland were delta 4-androstenedione-3 alpha, 17 beta-diol. Cells were isolated from the preputial gland...
Article
After intracardial injection of [1,2-3H] dehydroepiandrosterone ([3H]DHA) into female rats, [3H]DHA was found to accumulate and was metabolized in the preputial gland, but not in the diaphragm. The identified metabolites of [3H]DHA in the preputial gland were δ4-androstenedione-3α,17β-diol. Cells were isolated from the preputial gland after treatme...
Article
After the rat preputial gland was treated with collagenase and trypsin, five bands of cells were isolated by centrifugation in Ficoll gradients. Homogenates of the heavier cells (Bands IV and V) which contained less lipids, were more active than the homogenates of the lighter cells (Bands I, II and III) in transforming [1,2-3H]-dehydroepiandrostero...

Citations

... Finasteride is a type II 5-alpha-reductase inhibitor which decreases dihydrotestosterone (DHT) by about 65% in serum, prostate, and scalp. It was registered in Europe in 1992 for treatment of benign prostatic hyperplasia [14,15]. e drug became registered in the United States of America (1993) and Europe (1994) for AGA therapy (mild to moderate) in male patients [14,15]. ...
... 38,39 In fact, the structure of STS shows a hydrated FGly at position 75 linked to a sulfate moiety, presumably the resting state of the enzyme; 23 based on this finding, the reaction mechanism as depicted in Figure 2 appears likely. The catalytic site of STS features a bivalent cation, most likely a Ca 2 þ (as in arylsulfatase B 32 ), which is complexed by oxygen atoms of the hydrated FGly 75 and of Asp and Gln residues. Several histidine residues in the immediate vicinity may play important roles in catalysis as well, consistent with earlier biochemical studies. ...
... Sawaya et al reported greater 5-AR enzymatic activity increasing conversion of androgens to DHT at AGAaffected areas. 20 Moreover, sebaceous glands on balding scalps reveal higher binding affinity for DHT and express significantly higher ARs than healthy scalps. 13,14 Apart from promoting follicular miniaturization, DHT also upregulates sebocyte differentiation, leading to increased size of sebaceous glands in AGA-affected scalps. ...
... After regression by apoptosis in the catagen phase, they enter the telogen phase [10,11]. Apoptosis is a critical event in the regulation of the hair cycle as anagen hairs normally grow for 4-7 years in humans before the cycle enters into the resting phases of catagen and telogen [12,13]. During the process of hair follicles development, Wnt signalling plays a crucial role in hair follicle morphogenesis and regeneration [14,15]. ...
... Although other suspects or tools are likely to be discovered in the future, it cannot be excluded that, for each individual, the causal agent, as well as the sequence of events or combined factors, may be different. The large number of molecules claimed to be active and patented in this field, 89 and their limited efficacy in offering a definite and extensive cure of AGA, confirm that the mechanism of AGA is highly complex. Accordingly, it appears that, due to the complexity and multiple interactivities and cooperations involved throughout the distinct inflammatory pathways (partly described in Fig. 2), an anti-inflammatory strategy should be targeted to the appropriate effector(s) at the right moment. ...
... [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Twenty-four studies investigated gene expression profiling [18][19][20][21][22][23][24][25][26][27][28] and markers for AGA. [29][30][31][32][33][34][35][36][37][38][39][40][41] Fourteen studies focused on the action of 5-alpha reductase (5AR), which converts the androgen (testosterone) into dihydrotestosterone (DHT) and the inhibition of this enzyme 42-55 using enzymatic, radiochemical and cell proliferation assays. Thirteen studies used the same techniques to investigate the role of other enzymes in the mediation of AGA. ...
... In addition, the skin expresses all necessary enzymes to convert dehydroepiandrosterone sulfate (DHEAS) to dihydrotestosterone [25]. Aromatase also exists in sebaceous glands and the outer root sheath of hair follicles and can diminish local androgen action through aromatization [25,26]. ...
... 3 However, in AGA, due to the effect of the testosterone metabolite dihydrotestosterone on susceptible HFs, the anagen phase of HFs is gradually reduced while the telogen phase is prolonged. 4,5 This change results in HF miniaturization, 6 leading to a transformation from terminal to vellus-like hair in individuals with AGA. As the acknowledged target, dermal papillae (DPs) are the main sites of androgen activity in HFs. ...
... Some others were studied only in vitro or in animal models, so further investigations are needed. These studies are summarized in Table 1 [31][32][33][34][35][36][37][38][39][40]. ...
... Besides the above two therapies and, more successfully, hair transplantation, little else is effectively used to augment hair growth in AGA (3). This is partly because our knowledge of the pathogenesis is still meager and offers few rationale targets for therapy. ...