SUMMARY A competitive protein-binding assay of progesterone and a radioimmunoassay of total unconjugated oestrogens were evaluated and employed in the measurement of these steroids in the plasma of guinea-pigs at different times during the reproductive cycle. Production rates (PR) were calculated from the product of the endogenous steroid concentration and its metabolic clearance rate. During the oestrous cycle, plasma progesterone levels rose from undetectable levels at the time of ovulation to 2·8 ± 0·33 (s.e.m.) ng/ml 5 days later; PR was 0·26 mg/day. During pregnancy, plasma progesterone concentrations in post-partum mated guinea-pigs rose from 15 ng/ml at day 15 post coitum (p.c.) (PR, 0·65 mg/day) to a peak value of 329 ± 14 ng/ml by days 30 to 45. The concentration fell 51–55 days p.c. (160 ± 14·7 ng/ml), but rose before parturition to 258 ± 22 ng/ml. After day 20 p.c., PR was 1·24 ± 0·3 mg/day. After parturition, plasma progesterone levels fell rapidly and during lactation were about 10 ng/ml (PR, 0·4 mg/day). Total unconjugated oestrogens in arterial plasma were not detected in early pregnancy, but rose from values of 12·8 ± 1·9 pg/ml (days 31–35) to 31·0 ± 5·2 pg/ml (days 56–60). There was a slight fall before, and a rapid one after parturition. The ratio of progesterone to oestrogen in plasma fell during pregnancy and reached its lowest values between days 55 and 60.
The metabolic clearance rate (MCR) of progesterone was measured by continuous infusion of the tritium-labelled steroid in guinea-pigs under light sodium pentobarbitone anaesthesia. In normal animals during the oestrous cycle, the MCR was 112\m=.\8 \ m=+-\ 7\m=.\0 (S.E.) 1 plasma/day/kg. In pregnant animals there was a sharp decrease in MCR between days 15 and 20, to 8\ m=. \ 3\ m=+-\ 0\ m=. \ 81/ day/kg. This low clearance rate was observed throughout the remainder of gestation. After parturition MCR returned slowly to non-pregnant levels, reaching 85 1/day/kg by day 12 post partum.The decrease in metabolic clearance rate occurred at the same time as the increase in plasma concentration of progesterone. This may be related to an increase in binding proteins with a high affinity for progesterone. The stimulus for the decrease in MCR in pregnancy is obscure but appears to depend on the presence of a viable conceptus. In the non-pregnant guineapig the MCR is not reduced by exogenous oestrogen, hysterectomy or hypophysectomy.
A radioimmunoassay based on an antiserum to human parathyroid hormone-related protein PTHrP(1-16) was used with PTHrP(1-34) standard to measure the concentration of immunoreactive PTHrP in extracts of fetal parathyroid glands from lambs and calves and also placental membranes obtained from several species, including man. Dilution curves from these sources were parallel to those obtained for PTHrP(1-34) standard. It was demonstrated that this parallelism was not the result of tracer damage caused by enzymic activity in the tissue extracts. Extracts of human placental membranes were subjected to high-pressure liquid chromatography with a linear acetonitrile gradient. Co-elution of cytochemical biological activity with 125I-labelled PTHrP(1-34) was noted. These results provide further evidence for both the fetal parathyroid glands and the placenta containing material resembling PTHrP which may be responsible for sustaining the activity of the placental calcium pump which maintains the fetus hypercalcaemic relative to its mother.
Parturition in the guinea-pig is not preceded by any consistent change in the maternal plasma concentrations of progesterone, total unconjugated oestrogens or corticosteroids, or by a significant change in the concentration of progesterone-binding globulin (PBG). The onset of parturition was delayed by high doses of oestrogens (stilboestrol and oestradiol), but was not affected by oestriol or an antiserum raised against oestradiol. Premature parturition was achieved by the intra-carotid infusion of adrenocorticotrophin or prostaglandins (PGF2\g=a\, PGE2, I.C.I. 80,996) in conscious animals with indwelling catheters. I.C.I. 80,996, a potent analogue of PGF2\g=a\, induced parturition in all seven guinea-pigs treated; delivery occurred within 6 h of starting the infusion in six animals, and within 48 h in the seventh. The undesirable side-effects that accompanied treatment with PGF2\g=a\ or PGE2 were not encountered with I.C.I. 80,996. Parturition induced experimentally resembled normal delivery but was not preceded by any significant change in the maternal levels of progesterone, total unconjugated oestrogens, corticosteroids, PBG or CBG in the circulation. Oxytocin was not detected until the delivery of the first foetus.Parturition was not induced by maternal or foetal injections of corticosteroids or dexamethasone. Earlier findings are confirmed that the foetal adrenal grows steadily throughout late pregnancy and, unlike the foetal lamb adrenal, undergoes no rapid phase of growth immediately before term. Foetal adrenal weight decreased relative to foetal body weight.The trigger for parturition in this species remains unidentified.
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