Maintenance of Pregnancy by Synthetic Progestagens in Guinea-Pigs Ovariectomized Before Implantation; Progesterone-Binding Protein and Placental Progesterone Secretion

Abstract

In guinea-pigs ovariectomized before implantation, pregnancy can be maintained during the first 3 or 4 weeks, a critical period of early growth, by synthetic progestagens that do not metabolize to progesterone (norgestrel, medroxyprogesterone acetate and melengestrol acetate). It follows that peripheral plasma progesterone levels are related to placental progesterone secretion. There were indications that progesterone secretion by the placenta begins as early as day 16-18 of pregnancy. In the experimental animals the plasma progesterone levels, measured by a competitive protein-binding technique, were 9\m=.\4\ m=+-\ 2\m=.\07 ng/ml (mean \ m=+-\ S.E.M.; n = 18) by days 20-22 of pregnancy; they continued to rise and reached 26\m=.\4\ m=+-\ 3\m=.\88ng/ml (n = 8) by days 27 to 29.The metabolic clearance rate of progesterone measured in four pregnant ovariectomized animals with progesterone or progestagen implants, was < 10 1/day as in normal pregnant animals. The calculated production rates of progesterone in the experimental animals (0\m=.\1 to 0\m=.\35 mg/day) reflect the placental production rate of progesterone. A simple 'assay' is described for the high affinity progesterone-binding protein of pregnancy (progesteronebinding globulin).

Steroid Synthesis in Vitro by the Placenta of the Guinea-Pig. And Progesterone Concentrations in Systemic and Uterine Plasma

“…The progesteronecontributedbyeach placenta can be correlated tothe developmental changes of the SZ. Our results, as well as those of Illingworth & Deanesly (1972), indicate that the placenta may produce traces of progesterone as early as days 14-20 when the only tissues in the placental disk were the SZ and the GC (Davies, Dempsey & Amoroso, 1961). Pro¬ gesterone secretory activity of the placenta was initiated between days 20 and 25 since progesterone secretion by the placenta was considerable by day 25.…”

Onset of Synthesis of Progesterone by Ovine Placenta

“…Pregnancy maintenance in ovariectomized ewes In the study of Alexander & Williams (1968), the lowest dose of progesterone maintaining pregnancy in 100% of ovariectomized ewes was 1 -05 mg/kg per week and in certain bioassays the progestagenic activity of MPA is 30-to 40-fold greater than that of progesterone (Miyake & Pincus, 1958;Illingworth & Deanesly, 1972). The mean body weight of sheep in this study was 65 kg, thus the estimated maintenance dose of MPA was 1-7-2-3 mg/week.…”

“…Onset of secretion ofprogesterone The technique of ovariectomy and treatment with MPA has been used previously to assess placental progesterone production in the guinea-pig (Illingworth & Deanesly, 1972) and the bitch (Concannon, Powers, Holder & Hansel, 1977). One result of the present work was the demonstration that ovariectomy and treatment with MPA could be used to investigate the extra-ovarian contribution to progesterone levels in the circulation of sheep in early pregnancy.…”

Progesterone-Binding Globulin and Testosterone-Binding Activity in Guinea Pig Serum During Pregnancy: Relationship to Progesterone and Oestrogens

“…The steep rise in progesterone and PBG serum concentrations occurs concomittantly with the placental secretion of progesterone (days 16-18) as dis¬ cussed by lllingworth 8c Deansley (1972). Unlike other sex hormone binding serum proteins, the concentration of PBG shows no correlation to the level of endogenous oestrogens, neither can its production be induced by treating the non pregnant animal with exogenous oestradiol (Milgrom et al 1973;Lea 8c Stoa 1973, unpublished results).…”