Pituitary hormones and systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is known for its predominant occurrence in women and for its peak incidence during the reproductive years. The increased ratio of female to male SLE patients implies that sex-associated genetic and/or endocrine factors modulate disease proclivity and development. While chromosome differences or sex-associated metabolic or environmental factors may underlie the predominant occurrence of SLE in women, no relationship with the disease has proven stronger than those of female sex and female/male differences in sex hormones. This concept has been supported not only by epidemiologic studies, but also by substantial evidence of the immunoregulatory actions of 17 -estradiol (estradiol), testosterone, progesterone, dehydroepiandrosterone (DHEA)/ DHEA sulfate, and prolactin (1–4). A recent review and meta-analysis of data examining sex hormone abnormalities in SLE patients revealed that female SLE patients had significantly depressed concentrations of androgens and elevated concentrations of estradiol compared not only with their male counterparts with SLE but also with healthy controls (5). In addition, both female and male SLE patients had abnormally elevated serum prolactin concentrations, and in male SLE patients, elevation of serum prolactin concentrations was the only sex hormone aberration clearly identified in meta-analyses (5). Elevated prolactin concentrations in SLE patients (4,5), regulation of sex steroids by pituitary gonadotropins (6,7), interdependence of neuroendocrine and immune systems (8), and effects of inflammatory cytokines on pituitary function (9,10) evoke the possibility that pituitary hormone abnormalities contribute to or synergize with the altered sex steroids contributing to SLE disease expression. Investigations of pituitary hormones in SLE have been relatively uniform in their enrollment of patients and appropriately matched healthy controls. However, small numbers of study participants, variability in interand intrastudy results, long time intervals over which comparisons have been reported, and absence of sufficient statistical power to test respective hypotheses have limited the conclusions and possibly obscured the identification of important relationships between SLE and pituitary hormonal immunomodulation. Furthermore, peptide hormone/steroid/cytokine feedback loops, hormonal interconversions (e.g., DHEA to testosterone and/or estradiol), and the superimposed hourly, daily, and monthly chronobiologic variations of menses, pregnancy, and/or hormone administration complicate a simple interpretation of these cause-and-effect relationships as well as successful application of hormonal immunotherapy. We review herein the investigations of adenohypophyseal hormones—follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), growth hormone (GH), and prolactin—in patients with SLE. These anterior pituitary hormones are peptides of various molecular weights that bind to surface receptors and stimulate a variety of actions (6,7). They can affect the immune system directly (11) or indirectly through their effects on the synthesis of sex steroids with immunomodulatory capacity (1–4). Moreover, manipulation of serum pituitary hormones has been shown to be immunoregulatory, especially in animal models (11–15). In order to better understand the associations between SLE, sex, and pituitary hormones, clinical studies measuring serum concentrations of FSH, LH, ACTH, TSH, and GH (as well as prolactin) in nonpregnant adult women and men with SLE were identified by a computSupported by the Mississippi Lupus Association. Jing Li, MD, Warren May, PhD, Robert W. McMurray, MD: University of Mississippi Medical Center, Jackson. Address correspondence and reprint requests to Robert W. McMurray, MD, Division of Rheumatology and Molecular Immunology, L525 Clinical Sciences Building, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216. E-mail: Robert.McMurray@medicine.umsmed.edu. Submitted for publication March 9, 2005; accepted in revised form August 25, 2005.