Uteroglobin, a progesterone‐regulated secretory protein in rabbit uterus, was used as a marker protein for studies on progestational activity of various natural and synthetic androgens. All the androgens investigated were able to induce uteroglobin synthesis in rabbit uterus; some of the synthetic androgens were even better inducers than progesterone itself. Our results suggest that androgens elicit their regulatory action on uteroglobin synthesis by way of progestin receptor mechanism, since: (i) There was an intimate correlation between the in vitro binding affinity to progestin receptor and the in vivo potency of the androgens to induce uteroglobin synthesis; (ii) Androgens were able to translocate cytosol progestin receptors to uterine nuclei; (iii) Dose‐response curves for uteroglobin induction were parallel for androgens and progestins, and (iv) Flutamide, a non‐steroidal antiandrogen, did not abolish androgen‐induced synthesis of uteroglobin or androgen‐promoted nuclear translocation of cytosol progestin receptors. Both progesterone and androgens seem to control uteroglobin synthesis through mechanisms involving formation of new mRNA species, since in each case there was an increase in the uterine preuteroglobin‐mRNA activity, as evaluated by a cell‐free in vitro translation assay, which correlated with the amount of uteroglobin secreted into the uterine fluid. Some of the androgens studied (7α, 17α‐dimethyl‐19‐nortestosterone, 17α‐ethyl‐19‐nortestosterone and 11‐methylene‐17α‐methyl‐19‐nortestosterone) enhanced uteroglobin synthesis to the same or greater extent than progesterone. Interestingly, these steroids are also known to be very potent androgens. The progestational actions of androgens may be applicable to human tissues, too, since all the androgens investigated were bound by the human uterine progestin receptor in a fashion identical with the rabbit receptor.
Investigations were conducted to quantify activity of uteroglobin mRNA and secretion of uteroglobin in rabbit uterus after administration of progesterone and 5alpha-dihydrotestosterone, either alone or concomitantly with oestradiol-17beta and tamoxifen, a non-steroidal anti-oestrogen. Poly(A)-containing mRNA was isolated from the uterine tissue by extraction with phenol/chloroform, precipitation with ethanol and chromatography on oligo(dT)-cellulose. Cell-free translation in vitro of the poly(A)-containing mRNA was carried out in a wheat-germ lysate, and the product isolated by specific immuno-precipitation with anti-uteroglobin antiserum purified by affinity chromatography. Radioimmunoassay was utilized to determine uteroglobin content in the uterine flushings and tissue preparations. When given for 5 days, both progesterone (1mg/kg per day) and 5alpha-dihydrotestosterone (25mg/kg per day) elicited a marked induction of uteroglobin secretion, which was accompanied with accumulation of uteroglobin mRNA in the tissue. Concomitant administration of oestradiol-17beta (50mug/kg per day) or tamoxifen (12.5mg/kg per day) significantly decreased both progesterone- and 5alpha-dihydrotestosterone-induced uteroglobin secretion, with a parallel decrease in the uteroglobin-mRNA activity. The decline in the uteroglobin content of the uterine flushes brought about by oestradiol-17beta or tamoxifen administration was not due to inhibition of secretion of this protein by the endometrial cells, since a simultaneous decrease occurred in the tissue uteroglobin content. After a 5-day pretreatment with progesterone (1mg/kg per day), administration of oestradiol-17beta (50mug/kg per day) during the ensuing 4 days greatly accelerated the decay of the uteroglobin content in the uterine fluid.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.