Estren promotes androgen phenotypes in primary lymphoid organs and submandibular glands

As expected, the presence of functional ERs was mandatory for all the effects of E2. Similar to DHT-treatment, estren-treatment resulted in decreased thymus weight, as well as decreased frequency of bone marrow B cells. Treatment with estren or DHT also resulted in a shift in submandibular glands towards an androgen phenotype. All the effects of estren and DHT were independent of ERs.Our study is the first to show that estren has similar effects as the androgen DHT on lymphopoiesis in thymus and bone marrow, and on submandibular glands, and that these effects are independent of estrogen receptors. This supports the hypothesis of estren being able to signal through the androgen receptor.The effects of estrogens and androgens on the immune system in mice have been extensively studied. For example, B and T lymphopoiesis in bone marrow and thymus is suppressed by treatment with both estrogens [1-6] and androgens [7-9].Submandibular glands (SMG) are sexually dimorphic in rodents. The secretory activity of these glands is mainly localized to the acinar cells and the granular convoluted tubular (GCT) cells. The GCT cells are under hormonal control involving androgens, resulting in larger GCT in males compared to females [10-12].Signals from estrogens and androgens are transmitted into the target cells by the two known estrogen receptors (ERs), ERα and ERβ [13,14], or by the androgen receptor (AR), respectively.Postmenopausal hormone replacement therapy (HRT) has beneficial effects on the skeleton, but is associated with well-known side effects. This has lead to an increased focus on finding synthetic estrogen-like substances that only reproduce the beneficial effects of estrogen. 4-estren-3α,17β-diol (estren) is a synthetic compound with structural similarities to E2 that has been suggested to signal through both ERs and the AR [15-17].The aim of the present experiments was to investigate the estrogenic and androgenic effects of estren on lymphopoiesis in thymus and bone m