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ABSTRACT
Both production rate and metabolic clearance rate (MCR) of progesterone may vary rapidly and so effect short-term changes in blood concentration of the hormone. Here, a constant infusion and sampling technique was used to estimate these three characteristics of progesterone metabolism in seven conscious and ten anaesthetized rats on day 16 of pregnancy. After steady state was achieved, four samples were collected during a 1-h period from each rat. Mean values for production rate and MCR of progesterone in conscious rats were 14·0 ±1·4 μmol/day and 63·2 ± 6·2 litres/day respectively. Both values were substantially reduced in anaesthetized rats (8.6 ±0·8 μmol/ day and 39·4± 3·4 litres/day respectively) and so blood concentration was unchanged. The production rate was positively related to the total mass of luteal tissue (common correlation coefficient, r = 0·61, P <0·05). There were no consistent changes in the three characteristics with time but variation within rats was high. The estimated coefficients of variation for production rate, MCR and blood concentration within rats were 26, 18 and 17% in conscious and 27, 20 and 23% in anaesthetized rats respectively. Short-term changes in production rate and MCR generally were in the same direction (P <0·05). This reduced variation in blood concentration which would otherwise have occurred if production rate and MCR were unrelated. The pregnant rat is clearly capable of rapid shifts in production rate, MCR and blood concentration of progesterone and the positive relationship between production rate and MCR has a homeostatic effect on blood concentration.
J. Endocr. (1984) 102, 357–363
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SUMMARY
A modified venous outflow technique was used to measure ovarian blood flow in the rat. The rate of flow through the right ovary was 0·198 ± 0·009 (s.e.m.), 0·476 ± 0·076 and 0·958 ± 0·162 ml/min in six Day 0 (dioestrous), five Day 16 and six Day 22 pregnant rats respectively. The intravenous administration of 50 i.u. human chorionic gonadotrophin increased ovarian blood flow by 26 ± 4, 57 ± 19 and 46 ± 9% respectively, from 2 to 8 min after the injection. The present ovarian venous outflow results are substantially higher than those previously reported in the rat but agree with values determined with radioactive microspheres.
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We have sought to determine whether the rate of ovarian progesterone secretion in pregnant rats is inversely related to the arterial plasma progesterone concentrations. For this purpose, rates of ovarian progesterone secretion were measured on day 16 of pregnancy in seven progesterone-treated and eight untreated rats. Treated rats received once-daily s.c. injections of 63·6 μmol progesterone in peanut oil on days 13 to 16. In a separate experiment, this treatment was found to produce a relatively stable fivefold increase in plasma progesterone concentrations. The rate of ovarian blood flow was increased in treated animals (mean ± s.e.m.; treated, 0·63± 0·08 ml/min; untreated, 0·43± 0·08 ml/min) but the progesterone secretion rate was unchanged (treated, 1·13 ± 0·20 μmol/day per ovary; untreated, 1·05 ± 0·15 μmol/day per ovary). The stability of the progesterone secretion rate in the face of a fivefold increase in plasma progesterone concentration implies a lack of negative feedback from progesterone in plasma in the regulation of ovarian progesterone secretion.
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A venous outflow technique was used to monitor the rates of ovarian blood flow and progesterone secretion simultaneously during periods of 2–3 h in nine rats pregnant for 16 days and anaesthetized with sodium pentobarbitone. The rate of ovarian blood flow was 0·460 ± 0·135 (s.d.) ml/min and that of progesterone secretion was 27·2 ± 7·0 μg/h per ovary. Within rats, progesterone secretion was unrelated to the rate of ovarian blood flow (common correlation coefficient, r = 0·136; degrees of freedom = 61; P, not significant) but the latter was inversely related to the arterio-venous difference in the concentration of progesterone (r = −0·731; P <0·01).
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The role of placental luteotrophins in modulating plasma progesterone concentrations and ovarian progesterone secretion was examined in 16-day pregnant rats. In an initial experiment rats were placentectomized and their plasma progesterone concentrations monitored for 24 h; the rats were conscious within 30 min of placentectomy. Relative to control values, progesterone concentrations fell significantly within 0·5 h. A venous outflow technique was then used to monitor rates of progesterone secretion from ovaries of hysterectomized and control rats maintained under anaesthesia. Hysterectomy had no apparent effect on either progesterone secretion or plasma progesterone concentrations for at least 2 h. A final experiment was carried out to compare the effects of hysterectomy on plasma progesterone concentrations in conscious rats with those of placentectomized rats of the first experiment. Progesterone concentrations did not change significantly in hysterectomized rats for 4 h but fell to very low values by 24 h. These results suggest that placental luteotrophins do not have an acute, direct role in the control of plasma progesterone levels but are needed to maintain progesterone secretion in the longer term and possibly inhibit uterine luteolysin release.
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ABSTRACT
The basal concentrations of progesterone in plasma of 16-day pregnant rats were measured after seven different sampling procedures. Progesterone concentrations in serial samples from rats held at the time of sampling (restrained group) were compared with those obtained from rats allowed to remain free in their cage (free group). In addition, the effects on plasma progesterone concentrations of anaesthesia induced by ether or pentobarbitone sodium, and of adrenalectomy and/or ovariectomy were studied. Over the 8-h sampling period, progesterone concentrations in the plasma of restrained rats, with or without anaesthesia, were about 30% higher and more variable than those in free rats. Progesterone concentrations rose sharply over the first 30 min in restrained rats and in those treated with ether. Rats adrenalectomized the day before sampling did not show this early rise and their progesterone concentrations were similar to those of free rats. Progesterone concentrations were lowest in ovariectomized rats which had also been adrenalectomized. These findings show that adrenal secretion can increase plasma concentrations of progesterone in pregnant rats which have been handled or anaesthetized. Such a rise might well modulate the effects of experimental stimuli.
J. Endocr. (1984) 100, 189–193
