From: Billi Goldberg <bigoldberg@igc.apc.org>
Subject: Sex Hormones and the Immune System
Note: Copyright 1992, Dan R. Greening. Non-commercial reproduction allowed.
Archive-Number: 6627
Organization: unspecified
Date: Sun, 13 Dec 92 23:17:42 PST

               SEX HORMONES AND THE IMMUNE SYSTEM

The adrenal cortex synthesizes two classes of steroids: the 
corticosteroids (glucocorticoids and mineralocorticoids), and the 
androgens. The major corticosteroids (cortisol, corticosterone, and 
aldosterone) are shown together with the androgens 
(dehydroepiandrosterone, androstenedione, and testosterone). The 
corticosteroids are known to be immunosuppressive; androgens don't 
appear to be much better.

Testosterone has been proposed for use in HIV+ positive males since some 
individuals have low levels of this sex hormone. It has been stated that 
there have been no adverse effects in males from injections of 
testosterone. From the information below, maybe they should inject 
conjugated estrogens rather than testosterone.
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Encyclopedia of Immunology, Sex Hormones and Immunity, page 1371.

"There is also an effect of estrogen macrophages which are very 
important in processing and presenting antigen. Female rats have more 
macrophages than males. Estrogen treatment of male rats increases 
macrophage numbers. Estrogens are also potent stimulators of 
phagocytosis by macrophages and reticuloendothelial cells. The activity 
of macrophages varies with the estrus cycle. Estrogens modulate 
macrophage phagocytic activity and stimulate reticulo-endothelial cells. 
Estrogens enhance phagocytic clearance of immunoglobulin-coated 
erythrocytes, an Fc receptor dependent activity.

"Macrophages from estrogen treated animals show increased lysis of 
tumors and inhibit the growth of tumor cells. Testosterone has 
insignificant effects on macrophages. Estrogens stimulate production of 
IL-1 by macrophages as well as expression of Ia [MHC Class II] molecules  
on the surface of peritoneal macrophages."
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Hirasawa K; Enosawa S. Sex-associated differences in organ 
transplantation: different effects of steroid hormones, testosterone, 
estradiol, progesterone, and prednisolone on the survival time of 
allogeneic skin graft in rats treated with cyclosporin A. 
Transplantation Proceedings, 1991 Feb, 23(1 Pt 1):714-5. 

Abstract: Adult male recipients could accept allogeneic skin graft with 
CyA treatment alone for considerably long periods, whereas young male 
and female, and adult females were not susceptible to the 
immunosuppression. When testosterone or prednisolone was administered 
with CyA as a combination therapy to young male and adult female 
recipients, the survival time of the graft was significantly prolonged. 
On the contrary, estradiol totally inhibited the immunosuppressive 
activity of CyA in any recipients. These present data strongly suggested 
that immunoreactivity against transplantation antigens can be influenced 
by sex steroid hormones, and that the usage of steroid combination 
therapy may overcome the lack of immunosuppression by CyA induced by the 
female sex steroid estradiol.  
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Hirasawa K; Enosawa S. Effects of sex steroid hormones on sex-associated 
differences in the survival time of allogeneic skin grafts in rats. 
Evidence that testosterone enhances and estradiol reverses the 
immunosuppressive activity of cyclosporine. Transplantation, 1990 Oct, 
50(4):637-41. 

Abstract: Three-week-old DA (RT1a) male and female rats were pretreated 
with either orchiectomy or ovariectomy and administration of the 
opposite-sex steroid hormones, estradiol or testosterone. Skin from 
same-sex AO (RT1a) rats was then grafted when these pretreated rats 
reached 14 weeks of age, with a short course of immunosuppressive 
treatment of cyclosporine. The survival times of the grafts were 
reversed in that the male recipients pretreated to be like females 
acutely rejected the graft within 10 days as do normal adult female 
recipients. On the other hand, the female recipients  pretreated to be 
like males accepted the graft as do normal adult male recipients. In 
addition, the synergistic effects of either testosterone or estradiol 
with CsA on the survival time of the graft were examined. Testosterone 
successfully prolonged graft survival on normal adult female and young 
male recipients, but negligible prolongation was observed on young 
females. In contrast, estradiol abrogated the immunosuppressive activity 
of CsA and accelerated graft rejection in both male and female 
recipients. 
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Mendenhall CL; Grossman CJ; Roselle GA; Hertelendy Z; Ghosn SJ; Lamping 
K; Martin K. Anabolic steroid effects on immune function: differences 
between analogues. Journal of Steroid Biochemistry and Molecular 
Biology, 1990 Sep, 37(1):71-6. 

Abstract: As an untoward effect of chronic anabolic steroid use, 
immunologic alterations may be induced. To evaluate this possibility 
five commercially available steroids with various types of structural 
differences were studied in male Sprague-Dawley rats. Animals were 
divided into five groups  and treated with testosterone (Group 1), 
testosterone propionate (Group 2), testolactone (Group 3), oxandrolone 
(Group 4), and stanozolol (Group 5). Androgenic anabolic steroids were 
administered daily, subcutaneously dissolved in oil, at a dose of 1.1 
mg/kg. Immune alterations were assessed by skin-test responses to 
phytohemagglutinin. After five days of treatment (1.1 mg/kg/day) a 
significant immuno-suppression was observed with all groups. However, by 
day 10, groups 3, 4, and 5 showed an immuno-stimulation. Using 
oxandrolone as the model stimulant, serum testosterone levels were 
significantly suppressed, while castration abolished the stimulatory 
effect. These observations indicate that immune alterations do occur 
with anabolic steroids which are immuno-suppressive when the steroid 
nucleus is intact and immuno-stimulatory with nuclear alterations. It 
appears that these changes are associated with altered gonadal 
testosterone release. 
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