Gonadal steroids and immunity

Olsen, Nancy J.

doi:10.1210/er.17.4.369

Cited by 124 publications

(90 citation statements)

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“…For more than a century it has been recognized that androgen deprivation affects the immune system,34 and the GnRH receptor has been found on immune cells from humans35, 36 and rodents 13, 37. Interestingly, stimulation of the GnRH receptor exacerbated lupus in castrated female mice14, 38 and treatment with GnRH receptor antagonist delayed the onset of autoimmune diabetes15 and increased the survival rate among lupus‐prone mice 14.…”

Section: Discussionmentioning

confidence: 99%

“…It involves increased proliferation of immature thymocytes,34 but the exact mechanisms and the potential role of local GnRH receptors have not been clarified. Our study was consistent with previous literature in this field, except for leuprolide, which resulted in lower thymus and spleen weights compared to mice subjected to bilateral orchiectomy or degarelix.…”

Section: Discussionmentioning

confidence: 99%

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Differences in Hypercholesterolemia and Atherogenesis Induced by Common Androgen Deprivation Therapies in Male Mice

Poulsen

Mortensen

Koechling

et al. 2016

JAHA

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BackgroundTreatment of prostate cancer often involves androgen deprivation therapy (ADT) by gonadotropin‐releasing hormone (GnRH) receptor agonists, GnRH receptor antagonists, or orchiectomy. ADT may increase the rate of cardiovascular disease events, but recent clinical studies suggested that not all means of ADT carry the same risk, raising the possibility of non–testosterone‐mediated effects of different forms of ADT on atherosclerosis. Here we compared effects of ADT on atherosclerosis in intact and orchiectomized Apoe‐deficient mice.Methods and ResultsChow‐fed Apoe‐deficient mice were allocated to orchiectomy and/or monthly injections with the GnRH receptor agonist leuprolide or the GnRH receptor antagonist degarelix. Atherosclerosis was quantified at 26 weeks of age in the aortic arch by en face examination and in the aortic root by histology. In intact Apoe‐deficient mice, all types of ADT reduced testosterone production to castration levels. Although hypercholesterolemia was accentuated in leuprolide‐treated mice, the amount and composition of atherosclerosis was not different between the different types of ADT. In orchiectomized Apoe‐deficient mice, leuprolide, but not degarelix, augmented hypercholesterolemia, changed body, thymus, and spleen weights, and increased atherosclerosis in the aortic root. No direct effects of the drugs were detectable on cytokine secretion from murine bone marrow–derived macrophages or on splenocyte proliferation.ConclusionsNo differences in the development of atherosclerosis were detected among groups of intact Apoe‐deficient mice treated with different types of ADT. A pro‐atherogenic, possibly cholesterol‐mediated, effect of leuprolide was seen in orchiectomized mice that might be relevant for understanding the potential cardiovascular risk associated with GnRH agonist‐based ADT.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Differences in Hypercholesterolemia and Atherogenesis Induced by Common Androgen Deprivation Therapies in Male Mice

Poulsen

Mortensen

Koechling

et al. 2016

JAHA

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“…Testosterone, the immediate precursor of estradiol, is found in both men and women (14) and is generally accepted as being immunosuppressive (3,9). Most female-only SLE studies assessing serum estradiol also assessed serum testosterone concentrations; maleonly SLE studies typically assessed only testosterone or other androgens and not estradiol or progesterone (60,61) (Tables 1 and 3).…”

Section: Serum Testosteronementioning

confidence: 99%

“…However, the report in 1944 (5) of SLE flares corresponding to menstrual cyclicity focused an era of investigations on the potential contributions of estrogens, androgens, and prolactin to the development of SLE (6)(7)(8). Substantial evidence of immunoregulatory actions of 17␤-estradiol (estradiol), testosterone, progesterone, dehydroepiandrosterone/dehydroepiandrosterone sulfate (DHEA/DHEAS), and prolactin supports the concept that sex hormones modulate the incidence and severity of disease in patients with SLE (3,9).…”

Section: Introductionmentioning

confidence: 99%

Sex hormones and systemic lupus erythematosus: Review and meta‐analysis

McMurray¹,

May²

2003

Arthritis & Rheumatism

148

120

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“…During the reproductive years, females have a more robust humoral and cellular immune response compared to males [2]. This is reflected in observations showing that females possess a more developed thymus, higher antibody concentrations, and a greater capability to reject tumors [9]. Physiologic levels of estrogen, like those seen during the estrus/menstrual cycle, stimulate the immune response, whereas high levels of estrogen such as those found during pregnancy are suggested to downregulate cell-mediated immune responses [9].…”

Section: Introductionmentioning

confidence: 99%

Sex differences and estrogen modulation of the cellular immune response after injury

Bird¹,

Karavitis²,

Kovacs³

2008

Cellular Immunology

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Cell-mediated immunity is extremely important for resolution of infection and for proper healing from injury. However, the cellular immune response is dysregulated following injuries such as burn and hemorrhage. Sex hormones are known to regulate immunity, and a well-documented dichotomy exists in the immune response to injury between the sexes. This disparity is caused by differences in immune cell activation, infiltration, and cytokine production during and after injury. Estrogen and testosterone can positively or negatively regulate the cellular immune response either by aiding in resolution or by compounding the morbidity and mortality. It is apparent that the hormonal dysregulation is dependent not only on the type of injury sustained but also the amount of circulating hormones. Therefore, it may be possible to design sex-specific therapies to improve immunological function and patient outcome.

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Gonadal steroids and immunity

Cited by 124 publications

References 0 publications

Differences in Hypercholesterolemia and Atherogenesis Induced by Common Androgen Deprivation Therapies in Male Mice

Differences in Hypercholesterolemia and Atherogenesis Induced by Common Androgen Deprivation Therapies in Male Mice

Sex hormones and systemic lupus erythematosus: Review and meta‐analysis

Sex differences and estrogen modulation of the cellular immune response after injury

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