The nature of the proteins released together with progesterone from the bovine corpus luteum was investigated. Slices of bovine corpus luteum obtained at the mid-luteal stage of the oestrous cycle were incubated in vitro in the presence of bovine LH. Radioactive monitoring of compounds separated by gas–liquid chromatography showed that added [¹⁴C]acetate was converted to sterols and progesterone within the 2-h incubation period. Electrophoresis of the proteins recovered from the incubation medium showed the presence of a major band which migrated at the same rate as a progesterone-binding protein isolated from pooled corpora lutea. Densitometry revealed that the proteins in the incubation medium were enriched threefold in binding protein compared to those in an homogenate of corpus luteum. Equilibrium dialysis of the medium after addition of [³H]progesterone revealed the presence of a progesterone-binding activity (association constant = 10⁶l/mol) analogous to that contained in the cytosol fraction from bovine corpus luteum.

The finding that progesterone-binding protein is released concomitantly with the hormone has implications for the granule hypothesis of steroid secretion. The existence of an intracellular steroid-binding protein complex to maintain progesterone in high intragranular concentration would be predicted from this hypothesis.

ABSTRACT

The total (protein-bound plus free) and free concentrations of progesterone, oestradiol-17β and cortisol were measured serially throughout pregnancy in the plasma of two groups of women whose pregnancies went to term. Group A (n = 53) experienced an uneventful low-risk pregnancy with a spontaneous abortion rate of 8·6%. Women in group B (n = 22) were treated orally with medroxyprogesterone acetate (MPA; 80–120 mg daily) until 18 weeks gestation for threatened abortion within the first 6 weeks of pregnancy.

In both groups of women the proportion of each hormone circulating in the free or unbound form remained constant despite the overall increases which occurred in total circulating hormone concentrations as pregnancy progressed. The steroid hormonal profiles in the first half of pregnancy were similar in both groups of women. However, from weeks 20 to 40 total and free progesterone concentrations were significantly (P < 0·05 in each case) higher in group B compared with group A. Conversely, total and free oestradiol-17β concentrations were lower (P < 0·005 and P < 0·01 respectively) in group B. At this stage it is not known if these differences were attributable to the administration of MPA to women in group B or to altered placental steroidogenesis as a result of earlier uterine bleeding.

J. Endocr. (1985) 107, 293–300

ABSTRACT

The plasma concentrations of medroxyprogesterone acetate (MPA) in 14 women administered the progestagen for threatened abortion during the first 6 weeks of pregnancy were measured by specific radioimmunoassay. Treatment (52 nmol orally every 6 h) was continued to 18 weeks of gestation. The mean plasma concentration of MPA rose rapidly during day 1 of treatment to 14·1 ±1·84 nmol/l. It reached 21·5 ± 2·3 nmol/l by 7 days and subsequently stabilized at around 26·8±5·0 nmol/l by the end of week 2. Urinary steroid profiles were determined by gas–liquid chromatography and mass spectrometry for six of the MPA-treated women and compared with those of six untreated women of similar gestational age. No differences were detected between the two groups of women, suggesting that the administration of MPA during pregnancy did not alter qualitatively or quantitatively the metabolism and excretion into urine of progesterone and oestrogens.

J. Endocr. (1985) 104, 453–459

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

ABSTRACT

The synthetic progestagen, medroxyprogesterone acetate (MPA), was administered to sows in late pregnancy with the objective of slightly delaying the time of farrowing and thereby providing more marked associations between hormonal changes and the termination of pregnancy, and the initiation of farrowing and lactation in this species.

MPA was administered orally (140 mg, twice daily) to eight sows in late pregnancy on days 112, 113 and 114 of gestation. Parturition was then induced to occur on day 116 by injecting 200 μg cloprostenol i.m. on day 115 of gestation. The peripartum changes in the plasma concentrations of progesterone, cortisol, oestradiol-17β, relaxin, prolactin, lactose and 13,14-dihydro-15-keto prostaglandin F_2α (PGFM) were measured in these sows together with a group of untreated sows. The gestational length for the MPA-treated sows (116·3 ± 0·3 days, mean±s.e.m.) was significantly (P<0·01) greater compared with the untreated sows (114·9 ± 0·3 days). Plasma progesterone declined earlier (P<0·05) with respect to the time of parturition in the treated sows compared with the untreated group. With respect to the timing of parturition, the time at which maximal concentrations of relaxin were attained and the timing of the subsequent decline were earlier in the MPA-treated sows. In both groups of sows, the concentration of relaxin increased before the decline in plasma progesterone. In the untreated sows, the concentration of PGFM increased either slightly before or at the same time as the decline in plasma progesterone, whereas in sows treated with MPA, progesterone concentrations began to decline before any significant increase in the plasma concentration of PGFM. The profiles of cortisol, oestradiol-17β and PGFM were similar in both groups of sows. In both groups of sows, the timing of the initial increase in the concentration of plasma prolactin coincided with a similar rise in plasma lactose (P<0·01). Plasma progesterone either declined earlier or at the same time as the rise in plasma lactose (P<0·01) in the treated group of sows only.

We conclude that since the prepartum changes in the concentration of progesterone and relaxin occurred before significant changes in the concentration of PGFM in the MPA-treated sows, the nature of the luteolytic factor and the mechanism by which it exerts its action remains obscure. The higher concentration of lactose in the mammary secretion at birth in the MPA-treated sows compared with the untreated group suggested that lactogenesis was initiated earlier with respect to parturition following MPA treatment. Furthermore, the administration of MPA to sows in late pregnancy delayed the onset of parturition but did not inhibit lactogenesis.

Journal of Endocrinology (1990) 124, 475–484