Estren promotes androgen phenotypes in primary lymphoid organs and submandibular glands.
BACKGROUND
Estrogens and androgens have extensive effects on the immune system, for example they suppress both T and B lymphopoiesis in thymus and bone marrow. Submandibular glands are sexually dimorphic in rodents, resulting in larger granular convoluted tubules in males compared to females. The aim of the present experiments was to investigate the estrogenic and androgenic effects of 4-estren-3alpha,17beta-diol (estren) on thymus, bone marrow and submandibular glands, and compare the effects to those of 17beta-estradiol (E2) and 5alpha-dihydrotestosterone (DHT), respectively. Estrogen receptors (ERs) were blocked by treatment of mice with the ER-antagonist ICI 182,780; also, knock-out mice lacking one or both ERs were used.


RESULTS
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.


CONCLUSIONS
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.
Islander
Ulrika
U
Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborg University, Sweden. ulrika.islander@rheuma.gu.se
Hasséus
Bengt
B
Erlandsson
Malin C
MC
Jochems
Caroline
C
Skrtic
Sofia Movérare
SM
Lindberg
Marie
M
Gustafsson
Jan-Ake
JA
Ohlsson
Claes
C
Carlsten
Hans
H
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D002452:Cell Count; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D008221:Lymphoid Tissue / Q000187:drug effects* / Q000378:metabolism; D038041:Lymphopoiesis / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009919:Orchiectomy; D009928:Organ Specificity; D010052:Ovariectomy; D010641:Phenotype; D011944:Receptors, Androgen / Q000187:drug effects / Q000502:physiology; D011960:Receptors, Estrogen / Q000172:deficiency / Q000187:drug effects / Q000235:genetics; D012727:Sex Characteristics; D013363:Submandibular Gland / Q000187:drug effects* / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects* / Q000378:metabolism
C468666:4-estren-3,17-diol; D004963:Estrenes; D020847:Estrogen Receptor Modulators; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D013196:Dihydrotestosterone; D000077267:Fulvestrant; D004958:Estradiol