Identification of androgen receptor protein and 5alpha -reductase mRNA in human ocular tissues

Abstract

Background/aims-Androgens have been reported to influence the structural organisation, functional activity, and/or pathological features of many ocular tissues. In addition, these hormones have been proposed as a topical therapy for such conditions as dry eye syndromes, corneal wound healing, and high intraocular pressure. To advance our understanding of androgen action in the eye, the purpose of the present study was twofold: firstly, to determine whether tissues of the anterior and posterior segments contain androgen receptor protein, which might make them susceptible to hormone eVects following topical application; and, secondly, to examine whether these tissues contain the mRNA for types 1 and/or 2 5 -reductase, an enzyme that converts testosterone to the very potent metabolite, dihydrotestosterone. During the past several decades, it has become quite apparent that androgens exert a significant influence on the structural organisation, functional activity, and/or pathological features of many ocular tissues, including the lacrimal gland, meibomian gland, conjunctiva, cornea, lens, uvea, and/or retina. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] The nature of this hormone action appears to involve the regulation of such ocular factors as glandular morphology, gene expression, protein synthesis and secretion, lipid production, tear film stability, immune function, epithelial cell mitosis, aqueous outflow pathway characteristics, intraocular pressure, and vascular permeability. Methods-Human1-5 10 13-16 In addition, androgens have been proposed as a topical therapy for such conditions as aqueous deficient and evaporative dry eye syndromes, corneal wound healing, and glaucoma. However, despite these findings, very little information exists concerning the precise target cells for androgen action, the specific ocular processes controlled by these hormones, or the mechanisms underlying androgen-eye interactions in humans.The mechanism(s) by which androgens act on the human eye most likely involves the local, intracrine synthesis of these hormones from adrenal sex steroid precursors (that is, dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEA-S)) and a consequent androgen association with saturable, high aYnity, and steroid specific receptors in ocular tissues. 19The rationale for this hypothesis is twofold. Firstly, a large proportion of androgens in men, and the majority of these hormones in women, are produced in peripheral tissues from adrenal precursors. 18 In fact, humans and primates are unique in possessing adrenal glands that secrete large amounts of DHEA and DHEA-S, which are then converted into potent androgens and oestrogens by steroidogenic enzymes in peripheral sites and thereby permit target tissues to adjust the formation and metabolism of sex steroids to local requirements. 18 20 Secondly, androgen receptors, which are members of the steroid/thyroid hormone/retinoic acid family of ligand activated transcription factors, appear to mediate almost all of the "classic" actions ...

The Effects of Menopause and Hormone Replacement Therapy on Quality and Quantity of Tear, Intraocular Pressure and Ocular Blood Flow

“…Munaut et al [39]demonstrated the presence of β-type estrogen receptors and suggested that the sex steroid hormone axis may play a role in the pathogenesis of certain ocular diseases. It has also been reported that meibomian glands contain androgen, estrogen and progesterone receptor messenger RNA and protein within acinar epithelial cells [40, 41], that they express messenger RNAs for both type-1 and -2 5α-reductase [41]and respond to an androgen precursor by increasing production and release of lipids [42]. Sullivan et al [43]suggested that the meibomian gland is an androgen target organ and that androgens control meibomian gland function, regulate the quality and/or quantity of lipids produced by this tissue, and promote the formation of the tear film lipid layer.…”

Analysis of the Pathogenic Factors and Management of Dry Eye in Ocular Surface Disorders

“…Women are more likely to experience DE disease during certain periods of significant hormonal alteration, for example, during pregnancy, lactation, oral contraceptive use and after menopause, suggesting that DE may be related to sex hormones [36][37][38][39]. Receptor for androgens, progesterone, estrogen and prolactin has been found in several ocular tissues including the lacrimal gland and MG [36][37][38][39].…”

“…Androgens in fact, act on epitelia acinar cells that contain receptors for messenger RNA and/or protein receptors for androgens. These cells respond androgen binding it to specific lipid-producing area on the cell surface which then transcribes specified genes to increase the lipid layer distribution over the ocular surface [36][37][38][39]. In particular, Suzuki et al [38] demonstrated that testosterone stimulates genes related to lipid metabolic pathways and suppresses genes regulating epithelial keratinisation.…”

Complete Androgen Insensitivity Syndrome

“…[32][33][34][35] Furthermore, androgen effects on sebaceous gland function may be inhibited by exposure to antiandrogens 36,37 or by defects in androgen receptors (eg, CAIS). 38 In like manner, the meibomian gland contains androgen receptor protein within acinar epithelial cell nuclei, 24 and androgens seem to modulate gene expression and lipid production in this tissue. [1][2][3][4][5][6][39][40][41] These androgen effects seem to depend on the presence of intact androgen receptors 40,42 and may be attenuated by treatment with antiandrogen compounds.…”