Complete Androgen Insensitivity Syndrome

Abstract

To determine whether androgen receptors affect the fatty acid profiles of neutral and polar lipids in human meibomian gland secretions.Methods: Meibomian gland secretion samples were obtained from both eyes of (1) women with complete androgen insensitivity syndrome, a condition characterized by dysfunctional androgen receptors, and (2) agematched female and male controls. Samples were processed for high-performance liquid chromatography, mass spectrometry, or both and for analysis of the mass spectra of neutral and polar lipid fatty acid fragment ions by 3 different methods.Results: Androgen receptor dysfunction is associated with significant alterations in the appearance of nu-merous molecular species in the neutral and polar lipid fractions of meibomian gland secretions. The ability to detect these differences, and to assess their nature and extent, was facilitated by the use of several analytic approaches. Sex-related differences exist in the expression of a variety of neutral and, especially, polar fatty acid products in meibomian gland secretions.Conclusions: Androgens exert a significant effect on neutral and polar lipids in human meibomian gland secretions, and these hormonal effects may be mediated through androgen receptors.

Meibomian glands, meibum, and meibogenesis

“…The latter statement was corroborated in direct HPLC-MS experiments with human meibum (Butovich, 2009b; Butovich et al, 2007a; Butovich et al, 2007b), in which only exceedingly small amounts of TAG, and no true DAG, have been observed. Also, the m/z values reported by Sullivan et al (Krenzer et al, 2000; Sullivan et al, 2002a) as those of major lipid analytes were too small to be the signals of actual meibomian lipids: contrary to the authors' conclusions, there are no lipids in existence with m/z values between 100 and 200 such as those reported in Tables 2 and 3 and in Fig. 3 in (Sullivan et al, 2006), and in Tables 1 and 2 in (Sullivan et al, 2002a).…”

“…Also, the m/z values reported by Sullivan et al (Krenzer et al, 2000; Sullivan et al, 2002a) as those of major lipid analytes were too small to be the signals of actual meibomian lipids: contrary to the authors' conclusions, there are no lipids in existence with m/z values between 100 and 200 such as those reported in Tables 2 and 3 and in Fig. 3 in (Sullivan et al, 2006), and in Tables 1 and 2 in (Sullivan et al, 2002a). With all likelihood, those signals were either spontaneously formed fragments of actual lipids as a result of in-source fragmentation, or chemical or electronic noise generated by the instrument.…”

“…Initially, the project has been centered on the putative role of sex hormones in physiology and pathophysiology of MG. The effects of androgens, estrogen, and progesterone were evaluated in MG of humans, mice, and rabbits (Cermak et al, 2003; Darabad et al, 2013; Krenzer et al, 2000; Liu et al, 2016b; Richards et al, 2006; Rocha et al, 2000; Schirra et al, 2006a; Schirra et al, 2007; Schirra et al, 2006b; Schirra et al, 2005; Steagall et al, 2002; Sullivan et al, 2002a; Sullivan et al, 2006; Sullivan et al, 2000a; Sullivan et al, 2009; Sullivan et al, 1999a; Sullivan et al, 2002b; Sullivan et al, 2000b; Sullivan et al, 1999b; Suzuki et al, 2008; Wickham et al, 2000; Yamagami et al, 2002). It was reported that sex hormones induced rather convoluted changes in the gene expression patterns and lipid profiles of tested species.…”

Meibomian Gland Dysfunction in Primary and Secondary Sjögren Syndrome

“…We found that androgen deficiency in humans is associated with an increase in lid keratinization and the number of occluded and metaplastic meibomian gland orifices; reduced meibum quality; altered meibum lipid patterns; a decreased tear film breakup time; enhanced corneal fluorescein and conjunctival rose bengal staining; and increased DED symptoms [62-65, 68, 69]. …”

“…We discovered that androgens stimulate the function of this tissue, including increasing its lipogenesis and suppressing its keratinization [62-65, 70-76]. Indeed, dihydrotestosterone regulates the expression of thousands of genes in human meibomian gland epithelial cells, many of which are linked to lipid- and keratin-related activities [70].…”