Progestational Activity of Natural and Synthetic Androgens

Abstract

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.

Molecular Cloning and Characterization of Pregnancy Specific Protein Uteroglobin can Lead to Pregnancy Detection in Cattle- A Review

“…EPF due to the earliest serum benchmark for positive fertilization and hence successful conception. This novel pregnancy-specific protein has high immunosuppressive ability which is demonstrated by rosette inhibition test, a bioassay first demonstrated inpregnant mice [39,40] . Laleh et al demonstrated significant differences inrosette inhibition titers of pregnant and open cows with values being 8-10 and 3-5, respectively [41] .…”

Hormonal control of uteroglobin secretion in rabbit uterus. Inhibition of uteroglobin synthesis and messenger ribonucleic acid accumulation by oestrogen and anti-oestrogen administration

“…Uteroglobin (Beier, 1968) or blastokinin (Krishnan & Daniel, 1967) is a small secretory protein of rabbit uterus whose synthesis is induced by steroids with progestational activity (Beier, 1968;Urzua et al, 1970;Arthur & Daniel, 1972;Mayol & Longenecker, 1974;Torkkeli et al, 1977;Janne et al, 1978). In addition to progestins, natural and synthetic androgens were also shown to elicit induction of uteroglobin synthesis (Feigelson et al, 1977;Janne et al, 1978).…”

“…Uteroglobin (Beier, 1968) or blastokinin (Krishnan & Daniel, 1967) is a small secretory protein of rabbit uterus whose synthesis is induced by steroids with progestational activity (Beier, 1968;Urzua et al, 1970;Arthur & Daniel, 1972;Mayol & Longenecker, 1974;Torkkeli et al, 1977;Janne et al, 1978). In addition to progestins, natural and synthetic androgens were also shown to elicit induction of uteroglobin synthesis (Feigelson et al, 1977;Janne et al, 1978). Progesterone alone is sufficient to bring about stimulation of uteroglobin secretion (Urzua et al, 1970;Arthur & Daniel, 1972;Mayol & Longenecker, 1974;Torkkeli et al, 1977;Janne et al, 1978), whereas oestrogens alone elicit a minimal enhancement in the secretion of uteroglobin by the endometrial cells (Mayol & Longenecker, 1974;Feigelson et al, 1977;Torkkeli et al, 1977).…”

“…In addition to progestins, natural and synthetic androgens were also shown to elicit induction of uteroglobin synthesis (Feigelson et al, 1977;Janne et al, 1978). Progesterone alone is sufficient to bring about stimulation of uteroglobin secretion (Urzua et al, 1970;Arthur & Daniel, 1972;Mayol & Longenecker, 1974;Torkkeli et al, 1977;Janne et al, 1978), whereas oestrogens alone elicit a minimal enhancement in the secretion of uteroglobin by the endometrial cells (Mayol & Longenecker, 1974;Feigelson et al, 1977;Torkkeli et al, 1977). When administered along with progesterone, small amounts of oestrogens have been reported to potentiate the action of progesterone on uteroglobin secretion (Rahman et al, 1975), whereas higher doses of oestrogens seem Vol.…”

“…Hormonal control of uteroglobin induction seems to take place through synthesis of a specific mRNA, since, in general, the steroids that enhance uteroglobin secretion also bring about accumulation of utero-globin-mRNA activity (Beato & Nieto, 1976;Atger & Milgrom, 1977;Janne et al, 1978). As far as the action of oestrogens on the uteroglobin-mRNA activity is concerned, both increase (Beato & Nieto, 1976) and decrease (Atger & Milgrom, 1977) have been reported.…”