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PubMed1983

The effect of cortisol, progesterone, and transcortin on phytohemagglutinin-stimulated human blood mononuclear cells and their interplay.

The effect of transcortin on [3H]thymidine incorporation into phytohemagglutinin-stimulated human peripheral blood mononuclear cells and its influence on the well known suppressive effect of cortisol were investigated. Human transcortin by itself had no effect on thymidine incorporation between the concentrations of 0.25-1 X 10(-6) M. When transcortin was added to cortisol, the suppressive effect of cortisol decreased in proportion to the decrease in the protein-unbound cortisol concentration. We also investigated the influence of progesterone on transcortin-bound cortisol. When 0.5 and 1 X 10(-6) M transcortin, which contained 1 and 2 X 10(-7) M cortisol as a transcortin-bound form, were added to 5 X 10(-6) M progesterone, greater suppression of thymidine incorporation was observed that than produced by progesterone alone (86.1% and 81.3 for 0.5 and 1 X 10(-6) M transcortin, respectively). Moreover, when 5 X 10(-7) M transcortin containing the same amount of cortisol was added with 1, 2, and 5 X 10(-6) M progesterone, a greater suppression (92.6%, 74.1%, and 32.4% of control for 1, 2, and 5 x 10(-6) M progesterone) was demonstrated than that caused by progesterone alone (95.1%, 75.8%, and 49.5% of control for the corresponding concentrations of progesterone). This increased suppression was accompanied by an increase in the percentage of protein-unbound cortisol. These results indicate that unbound cortisol, whose concentration increases in the presence of progesterone, may be biologically active. The interaction between progesterone and cortisol may be modulated in part by the transcortin concentration.

Cells, Cultured↗

PubMed1990

The 24-hour pattern of the levels of serum progesterone and immunoreactive human chorionic gonadotropin in normal early pregnancy.

The purpose of this study was to characterize the levels of progesterone and hCG and the variability of those levels over 24 h in early pregnancy. Venous blood sampling was performed every 30 min during the first trimester of a subsequently normal pregnancy in 19 women. The variability in each progesterone and hCG data series was evaluated by three methods: 1) comparing the coefficient of variation (CV) of each individual hormone data set to the respective assay CV, 2) examining each data set for pulses, and 3) relating changes in hormone levels to the ingestion of a meal. The CV for each individual progesterone data set was greater than the assay CV (CV progesterone, 3.7%) in all subjects (range, 5.58-21.90%). The CV for each individual hCG data set was greater than the assay CV for hCG (CV hCG, 4.3%) in 17 of 19 subjects (range, 3.27-10.95%). Mean (+/- SE) progesterone and hCG peak frequencies were 2.4 +/- 0.3 and 1.7 +/- 0.3/24 h, respectively. When postprandial levels of progesterone were normalized to a percentage of preprandial levels, there were maximum decreases in mean progesterone levels of 15.4 +/- 2.6% and 13.1 +/- 1.9% 1 h after initiation of the lunch and dinner meals, respectively (P less than 0.05). Postprandial hCG levels decreased by 2.3 +/- 1.9% and 0.4 +/- 1.6% during this same time period (P greater than 0.05). These findings suggest that 1) both progesterone and hCG levels fluctuate during a 24-h period in early pregnancy; 2) this variability of both hormones is greater than inherent assay variability and can be resolved into a short term pattern of pulses, suggesting alterations in episodic secretion, metabolic clearance, or volume of distribution of the hormone; and 3) a portion of the variability in the progesterone time set may be due to the ingestion of meals.

Adult↗

PubMed1993

Progesterone 16 alpha-hydroxylase activity is catalyzed by human cytochrome P450 17 alpha-hydroxylase.

Progesterone and pregnenolone are metabolized to 17 alpha-hydroxysteroids by a cytochrome P450-dependent 17 alpha-hydroxylase (P450c17). The same enzyme can also catalyze the removal of the side-chain of these 17 alpha-hydroxylated steroids to yield androstenedione and dehydroepiandrosterone, respectively. We investigated the metabolism of progesterone by monkey kidney tumor (COS 1) cells transfected with a plasmid vector containing the cDNA encoding the complete amino acid sequence for human cytochrome P450c17. Transfected COS 1 cells converted progesterone to 17 alpha-hydroxyprogesterone as well as 16 alpha-hydroxyprogesterone, but no detectable androstenedione was produced. However, pregnenolone was converted to 17 alpha-hydroxypregnenolone and, ultimately, dehydroepiandrosterone. No 16 alpha-hydroxypregnenolone was produced. The kinetics of progesterone metabolism by the enzyme expressed in COS 1 cells indicated that both 17 alpha- and 16 alpha-hydroxylated products were products were produced from a common active site. Microsomes prepared from fetal adrenal and adult testis converted progesterone to 17 alpha-hydroxyprogesterone as well as 16 alpha-hydroxyprogesterone. No detectable androstenedione was produced by these preparations. Antibodies raised against porcine cytochrome P450c17 inhibited the 17 alpha- and 16 alpha-hydroxylation of progesterone to the same extent when using fetal adrenal microsomes, whereas no inhibition of 21-hydroxylation of progesterone was observed. Similar results were obtained with the imidazole antimycotic agent ketoconazole, which is a preferential cytochrome P450c17 inhibitor. From these results we conclude that human cytochrome P450c17 exhibits marked progesterone 16 alpha-hydroxylase activity in addition to its 17 alpha-hydroxylase function when expressed not only in a heterologous cell expression system but also, importantly, in human steroidogenic cells. Furthermore, the human enzyme has extremely low C-17,20-lyase activity toward progesterone, 17 alpha-hydroxyprogesterone, and 16 alpha-hydroxyprogesterone and fails to convert these to corresponding C19 steroids.

17-alpha-Hydroxyprogesterone↗

PubMed2005

Increased progesterone production during the luteal phase of menstruation may decrease anesthetic requirement.

UNLABELLED: Besides having important hormonal effects, progesterone has depressant and hypnotic effects on the brain. In this study, we compared women in the follicular phase with low progesterone levels and in the luteal phase with high progesterone levels regarding their anesthetic requirements. Twenty patients with menstrual cycle days from 1 to 10 (follicular group) and 20 patients with menstrual cycle days from 18 to 24 (luteal group) were included in the study. Anesthesia was induced with fentanyl and thiopental; relaxation was secured with rocuronium, and anesthesia was maintained with a mixture of nitrous oxide 2 L/min and oxygen 2 L/min plus sevoflurane. The delivered sevoflurane concentration was adjusted to sustain a constant bispectral index value that averaged 46 in both groups. To determine the progesterone levels, blood samples were taken from all patients before surgery. We found that progesterone levels were 0.86 +/- 0.30 ng/mL in the follicular group and 7.48 +/- 3.86 ng/mL in the luteal group. The minimum alveolar anesthetic concentration (MAC)-hour (MAC-h) value of sevoflurane in the follicular group (1.55 +/- 0.18 MAC-h) was significantly larger than in the luteal group (1.3 +/- 0.13 MAC-h) (P < 0.0001). The sevoflurane requirements were larger in the follicular group during the maintenance phase of anesthesia. In conclusion, high progesterone levels during the luteal phase might be the cause of decreased anesthetic requirement. IMPLICATIONS: The aim of this study was to determine the effect of high progesterone levels on anesthetic requirement. We measured progesterone levels before surgery and calculated the sevoflurane dose (MAC-h) required to maintain a constant bispectral index value. The dose of sevoflurane correlated inversely with serum progesterone concentrations.

Adolescent↗

PubMed2004

Effects of progesterone and norethisterone on cephalexin uptake in the human intestinal cell line Caco-2.

Little is known about the regulatory effects of steroid hormones on the intestinal H(+)/oligopeptide transporter PEPT1. In the present study, we investigated the effects of progesterone and its related compounds on the uptake of cephalexin, a typical PEPT1 substrate, using the human intestinal cell line Caco-2. Caco-2 cell monolayers were cultured on plastic cell culture plates coated with rat tail collagen type I. The determination of cephalexin uptake was performed with HPLC. To investigate the effect of progesterone treatment on cephalexin uptake, the monolayers were incubated with cephalexin after progesterone treatment. Progesterone decreased cephalexin uptake in a concentration-dependent manner, and the IC(50) value was calculated to be 2.3 microM. A significant decrease in cephalexin uptake was observed after progesterone treatment for 12 h, and the decrease was maximal when the monolayers were treated for 24-72 h. Cephalexin uptake was significantly inhibited by treatments with 17alpha-hydroxyprogesterone, norethisterone, and chlormadinone. By contrast, treatment with dehydroepiandrosterone, pregnenolone, estradiol, testosterone, hydrocortisone, and dexamethasone did not affect cephalexin uptake. The effects of progesterone and norethisterone treatment on the kinetic parameters of cephalexin uptake were investigated. The saturable component of cephalexin uptake was markedly inhibited by progesterone and norethisterone treatments. The J(max) of cephalexin uptake with progesterone and norethisterone treatments was significantly decreased compared with the control, whereas K(m) and K(d) values were not affected. Therefore the quantitative decrease in PEPT1 density is considered to be one cause of the decrease in cephalexin uptake with progesterone and norethisterone treatments.

Biological Transport↗

PubMed2005

Effect of progesterone on calcium activated potassium currents and intracellular calcium in guinea pig colon myocytes.

AIMS: To study the effects of progesterone on contractile activity of smooth muscle strips and on ion currents and intracellular Ca2+ ([Ca2+]i) intensity in single colonic myocytes in guinea pig proximal colons. METHODS: Strips and single cells were dissected from female guinea pig proximal colon. Contraction of strips through an isotonic transducer was assessed and the responsible currents to progesterone were recorded with EPC-9 amplifier in nystatin perforated whole-cell configuration. Detection of [Ca2+]i fluorescence loading fura-2 acetoxymethylester (fura-2/AM) was measured with confocal microscope. RESULTS: Progesterone significantly inhibited contraction of guinea pig colon strips in a dose-dependent pattern. Inhibitory concentration 50 (IC50) of progesterone in longitudinal strips and circular strips was, respectively, 9.7 microM and 1.0 nM. Iberiotoxin (IbTX) partially blocked inhibition of progesterone in both oriented smooth muscle strips. Ca2+ activated K+ (K(Ca)) channel currents recorded by depolarizing pulse protocol were enhanced by progesterone to 138% +/- 13% (n = 9, p < 0.01), and to 143% +/- 12% (n = 8, p < 0.01) when perfused with 10 mcM onapristone. Progesterone reduced L-Ca2+ currents to 67% +/- 6% (n = 7, p < 0.01) and had no effect with 5 microM nicardipine in bath solution. [Ca2+]i fluorescence was reduced by progesterone to 75% +/- 12% (n = 8, p < 0.01). CONCLUSION: Progesterone decreases the contraction of colonic smooth muscles by enhancing K(Ca) currents and reducing Ca2+ influx.

Animals↗

PubMed2004

Decline in lung function in patients with lymphangioleiomyomatosis treated with or without progesterone.

STUDY OBJECTIVE: Lymphangioleiomyomatosis (LAM), a disease affecting women and causing cystic lung lesions, and, in some instances, leading to respiratory failure and death, appears to be exacerbated by estrogens. Hence, hormonal therapy with progesterone is frequently employed; however, efficacy has not been demonstrated. Our aim was to determine whether progesterone administration slowed the decline in lung function in LAM. DESIGN: Retrospective study. SETTING: National Institutes of Health, Bethesda, MD. DESIGN AND SUBJECTS: The study population comprised 348 patients with LAM participating in a longitudinal research protocol. Declines in diffusion capacity of the lung for carbon monoxide (Dlco) and FEV(1) were measured in 275 patients observed for approximately 4 years. The declines in Dlco and FEV(1) of patients treated with progesterone, po (n = 67) or IM (n = 72), were compared with those of untreated patients (n = 136). MEASUREMENTS AND RESULTS: Overall yearly rates of decline in Dlco and FEV(1) were 2.4 +/- 0.4% predicted (0.69 +/- 0.07 mL/min/mm Hg) and 1.7 +/- 0.4% predicted (75 +/- 9 mL), respectively (mean +/- SEM). The most significant predictors of functional decline were initial lung function and age. After adjusting for initial FEV(1), age, and duration of disease, patients treated with IM progesterone tended to have lower rates of decline in FEV(1) than patients treated po (1.9 +/- 0.6% predicted vs 3.2 +/- 0.8% predicted, respectively; p = 0.081). However, there was no significant difference in rates of decline in FEV(1) between patients treated with IM progesterone and untreated patients (1.9 +/- 0.6% predicted vs 0.8 +/- 0.5% predicted, respectively; p = 0.520), and patients treated with po progesterone and untreated patients (3.2 +/- 0.8% predicted vs 0.8 +/- 0.5% predicted, respectively; p = 0.064). After adjusting for initial Dlco, rates of decline in Dlco were significantly higher in patients treated with po progesterone (3.6 +/- 0.7% predicted, p = 0.002) and IM progesterone (2.8 +/- 0.5% predicted, p = 0.022) than in untreated patients (1.6 +/- 0.6% predicted). CONCLUSIONS: Within the limitations of a retrospective study, our data suggest that progesterone therapy does not slow the decline in lung function in LAM.

Adult↗

PubMed1989

[The effect of RU486 and progesterone on luteal function during pregnancy].

In order to investigate the role of progesterone in the maintenance of pregnancy, an anti-progesterone agent, RU486 (RU) was injected subcutaneously into pregnant rats on day 12 (D12), and morphological changes of the uterus as well as endocrinological changes were observed. In all rats injected with RU, abortion occurred with macroscopic and microscopic intrauterine hemorrhage and degeneration or delivery of conceptuses. Endocrinologically, the levels of progesterone decreased rapidly 48 hours after the injection, while the levels of estradiol showed a tendency to increase. As progesterone is mainly produced by the corpus luteum but not by the placenta in rats, the decrease in progesterone is suspected to be due to luteolysis. Then in order to clarify the mechanism of luteolysis induced by RU and the effects of progesterone on this phenomenon, the dynamics of the luteotrophic factors (estradiol, LH, PRL) and specific binding capacity of the ovaries to LH/hCG were investigated in D7 pregnant rats treated with RU 1 mg/kg alone (RU group) or with both RU 1 mg/kg and progesterone 50mg/kg (RU + P group). The serum levels of progesterone in the RU group decreased significantly after 72 hours of administration, while those in the RU + P group remained within the levels of the control group. However, serum levels of luteotrophic factors in the RU group did not decrease, and some of them were even higher than those in the control group. In the RU + P group, luteotrophic factors remained within control levels. On the other hand, the specific bindings of LH/hCG to ovarian homogenates decreased significantly after 72 hours in the RU group. But in the RU + P group, the specific bindings were kept at the same levels as the controls. Scatchard analysis of these results disclosed that in the RU group, both affinity and numbers of receptors decreased compared to the controls, and that in the RU + P group only affinity decreased transiently and afterwards recovered quickly. From these results, it is concluded that deterioration of affinity and numbers of ovarian LH/hCG receptors seems to be one of the factors which induce luteolysis in pregnant rats treated with RU, and that progesterone can spare the effect of RU on the corpus luteum during pregnancy.

Animals↗

PubMed1983

Meiosis-inhibiting effects in vivo of antiserum to progesterone on follicular ova in immature rats treated with gonadotropins.

Effects of the neutralization of endogenous progesterone with rabbit antiserum to progesterone (anti-progesterone) on germinal vesicle breakdown of ova in follicles of small (less than 125 micrometers), intermediate (125-250 micrometers) and large (greater than 250 micrometers) diameter were examined by a quantitative histological technique. Immature rats were treated with 5 IU pregnant mare's serum gonadotropin (PMS) then with 10 IU human chorionic gonadotropin (hCG). Administration of anti-progesterone together with hCG 6 h later significantly decreased the incidence of germinal vesicle breakdown of ova in the large follicles, but not in the intermediate ones. This treatment did not affect the proportion of intermediate to large follicles in the population. Replacement with progesterone 1 h after the simultaneous injection of hCG and anti-progesterone partly reversed the reduced incidence of meiosis. An injection of rabbit antiserum to estrone, in addition to the replacement with progesterone 1 h after the simultaneous injections of hCG and anti-progesterone, restored the incidence of meiosis to a value comparable to the values found for control rats treated sequentially with PMS and hCG. We concluded that the hCG-induced preovulatory rise in progesterone has a limited but definite stimulatory effect on the resumption of meiosis in the ova of large follicles and that it mediates the meiosis-inducing action of hCG.

Animals↗

PubMed1975

Oestrogen-inducible uterine progesterone receptors. characteristics in the ovariectomized immature and adult hamster.

In order to characterize the uterine progesterone-binding proteins of oestrogen-primed and unprimed, ovariectomized immature and adult golden hamsters, cytosols were incubated with [3H]progesterone and/or other steroids and analyzed by sucrose-glycerol density gradient ultracentrifugation. Progesterone-binding components with sedimentation coefficients of 7S and 4.5S were found in the uterine cytosols, but not in the cytosols from the hypothalamus, pituitary, diaphragm, or small intestine. Oestradiol-17beta markedly elevated the level of 7S uterine receptor and this increase appeared to be due to new receptor synthesis, since actinomycin D and cycloheximide blocked this response. Fifty to 100 mug of oestradiol-17beta per kg body weight was found to promote a maximum increase in the 7S macromolecular component. The 7S receptor showed a tendency to saturate at 1 X 10(-7) M [1,2-3H]progesterone, indicating limited capacity. At a molar ratio of 100:1, unlabeled progesterone competed effectively for 7S and 4,5S [3H]progesterone binding, whereas 5alpha-pregnane-3,20-dione, oestradiol-17beta and testosterone did not. Moreover, [1,2-3H]cortisol and [1,2-3H]corticosterone did not bind to the 7S receptor, implying steroid specificity. CI-628, a non-steroid oestrogen antagonist, completely prevented [6,7-3H]oestradiol-17beta binding to its 8.5S uterine cytosol receptor, but was entirely without effect on 7S and 4.5S [3H]progesterone binding. Pronase, but not DNase or RNase, abolished 7S and 4.5S progesterone binding, suggesting that the binders are at least in part protein. Protamine sulphate and p-hydroxymercuribenzoate also obliterated 7S binding, implying that this receptor may be an acidic protein which contains sulfhydryl groups that are necessary for progesterone binding.

Animals↗

PubMed1980

Regulation of serum-progesterone in patients with essential hypertension.

Increased levels of progesterone in serum have been reported in male patients with essential hypertension (EH). We, therefore, investigated serum progesterone levels in relation to excretion of aldosterone after 4 days of low Na+ intake and 6 days following high Na+ diets, in 11 normotensive controls, 22 male patients with EH and 8 male patients with hypertension of renal origin (RH). In the group of normotensive controls, the concentration of progesterone in serum averaged 228 +/- 90 and 186 +/- 93 (mean +/- SD) pg/ml during low and high regimens of Na+ intake, respectively, despite a fall in the excretion of aldosterone from 22.8 +/- 9 to 1.8 +/- 1.4 microgram/24 h. Similarly, in patients with EH, serum progesterone remained unchanged during either low or high Na+ intake regimens: 197 +/- 73 and 219 +/- 83 pg/ml, respectively. In patients with RH, serum progesterone tended to be lower during both low and high Na+ diets: 167 +/- 61 and 185 +/- 72 pg/ml, respectively. In 5 normotensive controls, diurnal variations of progesterone and cortisol were significantly correlated (r = 0.726, p < 0.005). The results of the present study suggest, that progesterone is not involved in metabolism of Na+, either in normotensive or hypertensive male subjects. Correlation between circadian variations of progesterone and cortisol suggests, that progesterone levels are modified by ACTH secretion.

Adult↗

PubMed1985

Effects of oestradiol and prolactin on progesterone production by rhesus monkey luteal cells in vitro.

The effects of oestradiol and prolactin (Prl) on progesterone production by dispersed monkey luteal cells were examined. Corpora lutea were recovered from monkeys 5-7 days following ovulation induction during the puerperium. The tissue was dispersed by collagenase and mechanical disruption. The resulting cells were incubated in Dulbecco's modified Eagle's medium, containing the hormones to be tested, for 3 h at 37 degrees C. The medium was removed and assayed for progesterone by RIA. Human luteinizing hormone (hLH) produced a significant, dose-related increase in progesterone secretion that was comparable to that produced by dibutyryl cyclic adenosine monophosphate. Human follicle stimulating hormone (hFSH) had no effect upon progesterone production by the luteal cells. Oestradiol (100-10 000 pg/ml) produced a significant, dose-related decrease in both basal and hLH-stimulated progesterone production. Ovine Prl (oPrl) had neither a stimulatory nor an inhibitory effect upon basal progesterone secretion at doses up to 1000 ng/ml. Further, oPrl did not affect hLH-stimulated progesterone production. We conclude that oestradiol is a potent inhibitor of luteal progesterone secretion in vitro and that Prl does not inhibit progesterone production in the primate corpus luteum under these experimental conditions.

Animals↗

PubMed1991

Autonomous progesterone secretion from the bovine corpus luteum in vitro.

While the regulation of progesterone secretion from the corpus luteum by LH has been convincingly demonstrated, the secretory patterns in the absence of any pituitary LH inputs are yet unclear. Consequently, we investigated the progesterone secretion by an in vitro perifusion system to characterize spontaneous progesterone release from the isolated bovine corpus luteum. Slices (120 mg) of midluteal corpora lutea were placed in perifusion chambers and continuously perifused by Medium-199 for 160-320 min. Progesterone was determined by radioimmunoassay in the effluent fractions collected at 2-min intervals. The spontaneous progesterone release from all bovine corpora lutea was pulsatile. Pulses were observed at mean (+/- SEM) intervals of 17.7 +/- 1.5 min with amplitudes of 6.7 +/- 0.5 ng and release rates of 29.5 +/- 2.4 ng.ml-1.(2 min)-1 (N = 5). Addition of 6.7 nmol/l hCG to the perifusion medium appeared to increase the pulse amplitudes and release rates (195 +/- 25% over unstimulated conditions), but did not change the pulse frequencies (N = 3). Perifusions with calcium-free medium containing 50 mumol/l verapamil and 20 mmol/l EGTA tended to suppress the pulse frequencies and amplitudes of this spontaneous progesterone release, whereas addition of hCG reversed this decrease again (N = 3). When prostaglandin activity was inhibited by 100 mumol/l indomethacin added to the perifusion medium, both pulse frequencies and amplitudes of this progesterone release were enhanced (N = 4). During perifusions with 100 mumol/l of the anti-progesterone ZK 96.734, both the pulse frequencies and amplitudes increased (N = 4). These studies demonstrate an episodic progesterone release from the bovine corpus luteum perifused in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Follicle-stimulating hormone-testosterone interaction in modulating steroidogenesis in bovine granulosa cells. I. Effect on progesterone production.

The aim of this study was to investigate the effects of testosterone on basal and follicle-stimulating hormone (FSH)-induced progesterone production by cultured bovine granulosa cells. Granulosa cells were isolated from small (< 5 mm) and large (> 8 mm) follicles and cultured for 48 h in 1 ml of Medium-199 with different concentrations of FSH (0.1, 1, 10 and 35 mg/l). In addition, the combined effects of different amounts of testosterone (1 nmol-10 mumol) and 1 mg/l FSH for 48 h on progesterone production by granulosa cells of both groups of follicles were studied; progesterone production during the subsequent 24-h incubation period was evaluated in the absence of hormones. In a third experiment, granulosa cells were treated with 500 micrograms of dibutyryl-cAMP and 10 mumol of testosterone for 48 h. At the end of each incubation period, the progesterone content in the culture media was determined by a validated radioimmunoassay. Basal progesterone release during the 48-h incubation period was higher in granulosa cells from small as compared to cells from large follicles; in both groups of cells, progesterone production was stimulated maximally by 1 mg/l FSH. The treatment with 10 mumol of testosterone induced a decrease of progesterone production in both groups of cells, while lower amounts exerted an inhibitory effect only in cells from large follicles. Furthermore, 10 mumol of testosterone inhibited FSH-induced progesterone release, while lower dosages were ineffective. Dibutyryl-cAMP stimulated significantly the progesterone output by granulosa cells of both groups and testosterone was effective in suppressing this increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1976

Progesterone and 20 alpha-dihydroprogesterone in sheep: a model of their distribution and metabolism.

The rates of metabolism of progesterone and 20alpha-dihydroprogesterone (20alpha-diHP) in sheep have been measured during and after the infusion of tracer amounts of [3H]progesterone. There were significant differences in the blood concentration of [3H]progesterone between experiments, but these were not attributable to the stage of gestation or to the difference between pregnant and non-pregnant animals. The mean (+/- S.E.M.) metabolic clearance rate of progesterone was 3-277 +/- 0-239 litres blood/min. The simplest model of the distribution of progesterone was one containing two pools, V1[P] and V2[P], where [p] is the blood concentration of progesterone, and in 23 experiments on 7 sheep the mean pool dimensions were 7-8[P] mug and 70[P] mug, respectively. This model was developed to include the formation of 20alpha-diHP from progesterone. Progesterone appeared to be the major source of 20alpha-diHP, though this did not seem to be an obligatory metabolite. The parameters obtained gave comparably low residual deviations for both labelled steroids and were consistent with other observations made on progesterone clearance.

20-alpha-Dihydroprogesterone↗

PubMed1983

Concentrations of progesterone in the backfat of pigs during the oestrous cycle and after ovariectomy.

Small samples of backfat were taken daily during one oestrous cycle and more frequently after ovariectomy from 12 gilts by means of a simple biopsy technique and the levels of progesterone were determined. Compared to the levels of progesterone in peripheral plasma changes in backfat levels during the oestrous cycle were delayed by 1-2 days. Maximal levels with 89.7 +/- 9.2 (mean +/- s.e.m) ng progesterone/100 mg backfat were recorded on Day 15 of the oestrous cycle. It was estimated that, on this day, a total amount of about 36 mg progesterone is stored in the adipose tissue, which is approximately 200 times that present in total blood and corresponds to the daily production of the corpora lutea of the sow on Day 11. Initial half-life of progesterone in backfat after ovariectomy was estimated to be about 34 h compared to an initial half-life of plasma progesterone of about 120 min. The exact calculation of half-lives was, however, confounded by an obvious effect of anaesthesia or surgery on progesterone levels. Changes in backfat or plasma progesterone concentrations were not affected by the fat-to-lean ratio of the gilts. Fat progesterone levels determined in 44 additional pregnant and non-pregnant sows 17 or 20 days after mating indicated that reliable diagnosis of non-pregnant sows was possible on Day 20. It is concluded that the endocrinology of the oestrous cycle in pigs is related to the enormous storage of progesterone in the fat.

Adipose Tissue↗

PubMed1985

Immunosuppression, sialic acid, and sialyltransferase of bovine serum as a function of progesterone concentration.

Serum samples from progesterone-oestrogen-treated ovariectomized Holstein cows (N = 4) were compared with samples from control ovariectomized Holstein cows (N = 4) to determine the effects of physiological levels (0-6 ng/ml) of circulating progesterone. The average progesterone level in treated animals rose from 1 ng/ml (Day 0) to plateau at 5 ng/ml (Days 12 to 36). Sera from progesterone-oestrogen-treated cows during Days 4 to 10 significantly suppressed stimulation of lymphocytes by phytohaemagglutinin as compared with sera from control cows (P = 0.02), whereas no differences were detected in serum samples from Days 12 to 36. Serum samples from progesterone-oestrogen-treated or control cows did not affect the stimulation of lymphocytes by pokeweed mitogen. Sialyltransferase activity (P = 0.0002) and sialic acid content (P = 0.006) were both significantly elevated in serum from progesterone-oestrogen-treated animals compared with controls during Days 8 to 16, whereas no significant differences were observed at later times. The results suggest that suppression of phytohaemagglutinin-induced stimulation, sialic acid content, and sialyltransferase activity are sensitive not to the circulating level of progesterone but rather to increases in progesterone concentration, with maximal effects observed at Days 8, 12 and 12, respectively, after the start of progesterone treatment. The work provides a preliminary basis for further studies on the mechanism of immunosuppression by steroids and during pregnancy.

Animals↗

PubMed1989

Effect of ovine trophoblast protein-1, oestrogen and progesterone on oxytocin-induced phosphatidylinositol turnover in endometrium of sheep.

In Exp. 1, endometrium was collected from Day-15 cyclic ewes and effects of oTP-1, oxytocin and oTP-1 + oxytocin, in various temporal relationships, on phosphatidylinositol (PI) turnover were determined. Co-treatment of endometrium with oTP-1 and oxytocin inhibited stimulatory effects of oxytocin, while treatment with oTP-1 before and during oxytocin administration had no effect. Turnover of PI was unaffected by oTP-1 alone. In Exp. 2, ovariectomized ewes were treated with progesterone (50 mg/day) for 10 days and then oestrogen (100 micrograms/day) for 2 days and endometrium was collected. Oxytocin stimulated PI turnover in endometrium, but oTP-1 had no effect alone or in combination with oxytocin. In Exp. 3, ovariectomized ewes were treated with corn oil (1 ml/day), oestrogen (50 micrograms/day), progesterone (50 mg/day) or progesterone + oestrogen for 10 days and endometrium was collected. Oxytocin stimulated PI turnover only in ewes that received progesterone. oTP-1 alone had no effect on PI turnover, while co-treatment of endometrium with oxytocin and oTP-1 stimulated PI turnover in ewes treated with progesterone, but not progesterone and oestrogen. Pretreatment of endometrium with oTP-1 stimulated PI turnover when ewes were treated with progesterone or progesterone + oestrogen. Pretreatment of endometrium with oxytocin and then treatment with oTP-1 inhibited PI turnover compared to treatment with oxytocin alone. In Exp. 4, ovariectomized ewes were treated as in Exp. 2. Catheters were placed into the uterine horns and ewes received oTP-1 into one horn and serum into the other twice daily on Days 10-12 of steroid treatment. Endometrium collected on Day 13 was used to measure PI turnover and received either no treatment or oxytocin. Oxytocin stimulated PI turnover in endometrium of these ewes and in-vivo treatment of the ewes with oTP-1 had no effect on PI turnover. These results indicate that antiluteolytic effects of oTP-1 are not mediated by inhibiting effects of oxytocin on phosphatidylinositol turnover if oxytocin receptors are present and that uterine responsiveness to oxytocin is progesterone dependent.

Animals↗