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PubMed1996

Changing dose of progesterone results in sudden changes in frequency of luteinizing hormone pulses and secretion of 17 beta-estradiol in bovine females.

The aim of the present study was to elucidate the time course according to which changes in circulating concentrations of progesterone influence pulsatile secretion of LH and secretion of 17 beta-estradiol. Our working hypothesis was that changing the dose of progesterone would result in changes in frequency of LH pulses and secretion of 17 beta-estradiol within 72 h. Five days after behavioral estrus, thirty-three cows were randomly assigned to one of five groups: 1) control, no treatment (CONT, n = 5); 2) treatment with two progesterone-releasing intravaginal devices (PRIDs) for 11 days (2PRID, 5-6 ng/ml plasma progesterone, n = 7); 3) treatment with a 0.5 PRID for 11 days (0.5PRID, 1-2 ng/ml plasma progesterone, n = 7); 4) treatment with 2 PRIDs for 8 days followed by treatment with a 0.5 PRID for 3 days (2-0.5PRID, n = 7); and 5) treatment with a 0.5 PRID for 8 days followed by treatment with 2 PRIDs for 3 days (0.5-2PRID, n = 7). Cows subject to PRID treatments received injections of prostaglandin F2 alpha on Days 1 and 2 (Day 0 = day of initiation of PRID treatments, fifth day of the estrous cycle in CONT cows) to lyse the existing corpus luteum. Cows were bled for 12 h at 15-min intervals on Day 7.5 of the treatment period (twelfth day of the estrous cycle in CONT cows). The dose of progesterone was changed on Day 8 in cows that were assigned to the 2-0.5PRID and 0.5-2PRID groups, and blood collections continued an additional 72 h to characterize profiles of circulating concentrations of LH and 17 beta-estradiol. Cows treated with a 0.5 PRID had a greater (p < 0.05) number of LH pulses and higher (p < 0.05) concentrations of 17 beta-estradiol throughout the entire blood collection period than cows in the 2PRID and CONT groups. An increase in the number of LH pulses was detected within 6 h after the change from the high to the low dose of progesterone (2-0.5PRID), and frequency of LH pulses was similar to that of cows in the 0.5PRID group for the remainder of the period of blood collection. LH pulse frequency declined within 6 h after the shift from the low to the high dose of progesterone (0.5-2PRID) and was similar to that of cows in the 2PRID group by 12 h after the dose was changed. Within 6 h after the dose of progesterone was changed, circulating concentrations of 17 beta-estradiol increased (p < 0.05) in cows shifted from the high to low dose (2-0.5PRID) and declined (p < 0.05) after the dose of progesterone was changed from low to high (0.5-2PRID). We conclude that changing the circulating concentrations of progesterone concurrently affects frequency of pulsatile LH release and secretion of 17 beta-estradiol within 6-24 h.

Administration, Intravaginal↗
PubMed2002

Effects of progestins on progesterone synthesis in a stable porcine granulosa cell line: control of transcriptional activity of the cytochrome p450 side-chain cleavage gene.

The purpose of the present study was to examine the effects of progestins on progesterone synthesis and expression of the cytochrome P450 cholesterol side-chain cleavage gene (P450(scc)) in a stable porcine granulosa cell line, the JC-410. Cells were incubated for 48 h with the synthetic progestogen-levornorgestrel with or without RU486 (progesterone and glucocorticoid receptor antagonist) or RWJ26819 (progesterone agonist without affinity to glucocorticoid receptors). Both levonorgestrel and RU486 enhanced progesterone accumulation in a dose-dependent manner. RU486 did not antagonize the effects of levonorgestrel, and RWJ26819 had no effect on progesterone production in cultured JC-410 cells. Progesterone and levonorgestrel increased steady state P450(scc) mRNA levels after 3-6 h of treatment. Progesterone and RU486 at 0.1, 1, and 10 microM increased the transcription rate of P450(scc) transiently expressed in JC-410 cells after 18 h of incubation; 30 microM had no effect, and 100 microM suppressed transcription. Levonorgestrel did not affect transcription of the P450(scc) gene, and RWJ26819 reduced its transcription. Progesterone and RU486 significantly decreased the number of cells and total protein content after 72 and 24 h of incubation, respectively. Levonorgestrel had no effect, whereas RWJ26819 increased (24 h) but subsequently reduced (72 h) cell number and protein content. The present results indicate that progestins are capable of directly modulating progesterone biosynthesis in porcine JC-410 granulosa cells. These effects may be exerted in part through the regulation of P450(scc) gene expression. Ostensible differences exist between progesterone and its synthetic analogues in the control of progesterone secretion in the stable porcine granulosa cell line in vitro.

Animals↗
PubMed2006

Gonadectomy and progesterone treatment induce protection in murine cysticercosis.

The effects of progesterone on castrated mice of both sexes infected with Taenia crassiceps cysticerci were studied. Gonadectomy and treatment with progesterone before infection decreased parasite loads by 100% compared with intact uninfected mice. mRNA levels of IFN-gamma and IL-2 (typically associated to Th1-like profiles) were markedly decreased in infected gonadectomized (Gx) mice, whereas progesterone treatment of infected Gx mice did not affected its expression. mRNA levels of IL-4, and IL-10 (typically associated with Th2-like profiles) were reduced by gonadectomy, whereas restitution with progesterone did not affected this pattern in infected Gx progesterone-treated mice. Infection markedly induced expression of progesterone receptor isoform A in splenocytes of Gx mice (5-fold), whereas isoform B had no changes. Progesterone metabolism to dehydroepiandrosterone (DHEA) in Gx animals was increased 3-fold only in infected progesterone-treated uninfecteds of both sexes, but was not detectable in infected Gx progesterone-treated mice. Conversely, DHEA levels increased 100-fold in infected Gx progesterone-treated mice. However, androgen receptor expression in splenocytes of male mice showed a reduction by gonadectomy, and by infection, whereas in females AR expression showed no changes in the different mouse groups. These results suggest that progesterone, through its metabolism to DHEA, negatively affects the establishment, growth, and reproduction of Taenia crassiceps, by a mechanism that does not implicate a classic genomic pathway involving a nuclear androgen receptor.

Adjuvants, Immunologic↗
PubMed2006

Milk progesterone profile at and after artificial insemination in repeat-breeding cows: effects on conception rate and embryonic death.

The aim of this study was to investigate whether the skim milk progesterone concentrations at artificial insemination (AI) and day of rise of post-ovulatory progesterone concentration thereafter affect the conception and embryonic death rates in repeat-breeding cows. Milk samples were obtained from 96 repeat-breeding cows that failed to conceive to three or more AIs. The samples were taken from the cows at the day of AI and three times/week until day 45 post-AI. Skim milk was obtained after centrifugation and used for progesterone assay. The cows with a progesterone concentration more than 0.5 ng/ml at AI showed a significantly higher incidence of late embryonic death than those having a progesterone concentration<0.5 ng/ml at AI (p<0.01). As the progesterone level at insemination rose, conception rate declined. A negative correlation was shown between conception rate and skim milk progesterone level at AI. Of 56 cows showing a rise of progesterone to 1 ng/ml or more within 6 days after AI, 28 cows (50%) conceived. On the contrary, only eight of 39 cows (20.5%) conceived when the progesterone rose up to 1 ng/ml after day 6 post-AI. We concluded that increased progesterone concentration at the time of AI and delayed rise of progesterone post-AI might lead to decrease in fertility in repeat-breeding cows.

Animals↗
PubMed1991

Effects of the antiandrogen hydroxyflutamide on progesterone secretion by preovulatory rat follicles in vivo and in vitro.

Serum and ovarian progesterone levels and in vitro production of progesterone by preovulatory follicles were measured on proestrus in pregnant mare's serum gonadotropin (PMSG) primed immature rats in which the luteinizing hormone (LH) surge and ovulation were blocked by administration of the antiandrogen hydroxyflutamide. Serum progesterone levels observed at 12:00 on proestrus were significantly elevated, twofold above those observed in vehicle-treated controls, by in vivo administration of 5 mg hydroxyflutamide 4 h earlier. In control rats, proestrous progesterone did not increase until 16:00, in parallel with rising LH levels of the LH surge. No LH surge occurred in the hydroxyflutamide-treated rats, ovulation was blocked, and serum progesterone declined throughout the afternoon of proestrus, from the elevated levels present at 12:00. Administration of human chorionic gonadotropin (hCG) at 11:00 advanced the elevation of serum progesterone by 2 h in vehicle-treated controls and prevented the decline in progesterone levels in hydroxyflutamide-treated rats. The patterns of change in ovarian tissue concentrations with time and treatment were essentially similar to those observed for serum progesterone. In in vitro experiments, progesterone secretion during 24 h culture of preovulatory follicles obtained on PMSG-induced proestrus was significantly increased, sixfold, by addition to the culture media of 370 microM but not of 37 microM hydroxyflutamide. Testosterone (50 nM) and hCG (20 mIU/mL) caused 26- and 14-fold increases, respectively, in progesterone secretion by cultured follicles. Hydroxyflutamide significantly reduced the stimulatory effect of testosterone but not of hCG on progesterone secretion in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen Receptor Antagonists↗
PubMed1996

Progesterone induces changes in sleep comparable to those of agonistic GABAA receptor modulators.

There is much evidence that progesterone has hypnotic anesthetic properties. In this vehicle-controlled study, we examined the effects of three doses of progesterone (30, 90, and 180 mg/kg) administered intraperitoneally at light onset on sleep in rats. Progesterone dose dependently shortened non-rapid eye movement sleep (NREMS) latency, lengthened rapid eye movement sleep (REMS) latency, decreased the amount of wakefulness and REMS, and markedly increased pre-REMS, an intermediate state between NREMS and REMS. Progesterone also elicited dose-related changes in sleep state-specific electroencephalogram (EEG) power densities. Within NREMS, EEG activity was reduced in the lower frequencies (< or = 7 Hz) and was enhanced in the higher frequencies. Within REMS, EEG activity was markedly enhanced in the higher frequencies. The effects were maximal during the first postinjection hours. The concentrations of progesterone and the progesterone metabolites 3 alpha-hydroxy-5 alpha-pregnan-20-one and 3 alpha-hydroxy-5 beta-pregnan-20-one, both positive allosteric modulators of gamma-aminobutyric acid A (GABAA) receptors, were determined at different time intervals after vehicle and 30 or 90 mg/kg progesterone. Progesterone administration resulted in dose-dependent initially supraphysiological elevations of progesterone and its metabolites in the plasma and brain, which were most prominent during the first hour postinjection. The effects of progesterone on sleep closely resemble those of agonistic modulators of GABAA receptors such as benzodiazepines and correlate well with the increases in the levels of its GABAA agonistic metabolites. These observations suggest that the hypnotic effects of progesterone are mediated by the facilitating action of its neuroactive metabolites on GABAA receptor functioning.

Animals↗
PubMed1990

Progesterone as a bone-trophic hormone.

Experimental, epidemiological, and clinical data indicate that progesterone is active in bone metabolism. Progesterone appears to act directly on bone by engaging an osteoblast receptor or indirectly through competition for a glucocorticoid osteoblast receptor. Progesterone seems to promote bone formation and/or increase bone turnover. It is possible, through estrogen-stimulated increased progesterone binding to the osteoblast receptor, that progesterone plays a role in the coupling of bone resorption with bone formation. A model of the interdependent actions of progesterone and estrogen on appropriately-"ready" cells in each bone multicellular unit can be tied into the integrated secretions of these hormones within the ovulatory cycle. Figure 5 is an illustration of this concept. It shows the phases of the bone remodeling cycle in parallel with temporal changes in gonadal steroids across a stylized ovulatory cycle. Increasing estrogen production before ovulation may reverse the resorption occurring in a "sensitive" bone multicellular unit while gonadal steroid levels are low at the time of menstrual flow. The bone remodeling unit would then be ready to begin a phase of formation as progesterone levels peaked in the midluteal phase. From this perspective, the normal ovulatory cycle looks like a natural bone-activating, coherence cycle. Critical analysis of the reviewed data indicate that progesterone meets the necessary criteria to play a causal role in mineral metabolism. This review provides the preliminary basis for further molecular, genetic, experimental, and clinical investigation of the role(s) of progesterone in bone remodeling. Much further data are needed about the interrelationships between gonadal steroids and the "life cycle" of bone. Feldman et al., however, may have been prophetic when he commented; "If this anti-glucocorticoid effect of progesterone also holds true in bone, then postmenopausal osteoporosis may be, in part, a progesterone deficiency disease."

Animals↗
PubMed1977

In vivo progesterone treatment enhances [3H]estradiol retention by neural tissue of the female rat.

[3H]Estradiol retention was examined for neural tissues of ovariectomized rats as a function of various progesterone pretreatments. Short-term progesterone pretreatment (6 or 24 h) with a 50 mg pellet of progesteron sc resulted in increased in vivo retention of [3H]estradiol when measured at 6 or 24 h following withdrawal of the progesterone source. This increase was greatest in arcuate-median eminence tissue. A less pronounced increase was seen in the preoptic-anterior hypothalamus and cerebral cortex, and no increase was seen in the amygdala or mammilary bodies. Following long term progesterone pretreatment increased [3H]estradiol retention was observed in vivo at 48, 72, 96 or 120 h in the continued presence of the progesterone source for arcuate-median eminence, preoptic-anterior hypothalamus, amygdala and cerebral cortex. Also, when progesterone pretreatment was 24 h, [3H]estradiol retention was still increased at 36, 48, 60 and 72 h following removal of the progesterone source for arcuate-median eminence, preoptic-anterior hypothalamus, amygdala and cerebral cortex. Our demonstration that progesterone pretreatment can significantly increase [3H]estradiol retention by neural tissue suggests a possible mechanism by which progesterone can regulate the timing of ovulation and sex behavior. Furthermore, our observations are in keeping with the finding that progesterone has little or no effect at the organismal or tissue level unless estrogen is present.

Amygdala↗
PubMed1982

Combined effects of progesterone and tamoxifen in the chick oviduct.

Tamoxifen, an antiestrogen with no estrogenic effect on growth, differentiation, and egg white protein synthesis in the chick oviduct, has been administered together with progesterone. In estrogen differentiated, hormone-withdrawn animals, biochemical and ultrastructural data indicated that the combined treatment with progesterone plus tamoxifen increased conalbumin (+100%) and ovalbumin (+30%) more than progesterone alone and displayed estrogen-like growth-promoting properties (+50% in DNA content per oviduct). Moreover, when administered with progesterone and estradiol, tamoxifen lost part of its antiestrogenic activity. No obvious change of progesterone clearance from the blood or progesterone metabolism was recorded. The presence of progesterone in amounts similar to those resulting in optimal activity when injected alone (greater than or equal to 1 mg/kg) was necessary to obtain progesterone plus tamoxifen effects. The simultaneous presence of progesterone and tamoxifen was required in order to observe their combined effects, and it was observed that progesterone did not have to commit cells on which tamoxifen could subsequently act. In the immature "undifferentiated" oviduct, contrary to the effects of tamoxifen and progesterone alone, their combination induced cytodifferentiation of tubular gland cells which synthesized conalbumin and ovalbumin, an event never observed before in the absence of estrogen. These results support the suggestion that the hormonal milieu interferes with antiestrogen action.

Animals↗
PubMed1991

Involvement of protein kinase C in regulating tumor necrosis factor alpha-stimulated progesterone production in rat preovulatory follicles in vitro.

Tumor necrosis factor alpha (TNF) increased progesterone production in preovulatory rat follicles in vitro. More than 1 h in the presence of TNF was needed to enhance progesterone secretion, which was only seen after 24 h of culture. Neither cAMP nor cGMP levels in media and follicles increased either at short (5-20 min) or long periods (6-24 h) after TNF stimulation. The protein kinase C (PKC) inhibitor, H-7, blocked TNF-stimulated progesterone in a dose-dependent manner (1-300 mM), with 50% inhibition corresponding to 5.2 microM H-7, it also blocked LH-stimulated progesterone production, but higher doses were needed (50% inhibition corresponding to 54.5 microM H-7). However, the cAMP- and cGMP-dependent protein kinase inhibitor, HA1004, did not block TNF stimulated progesterone. The PKC activator, phorbol 12-myristate 13-acetate (PMA), increased progesterone maximally at 32 nM and above. Low doses of PMA in combination with TNF increased progesterone levels above that stimulated by PMA alone; however with the highest does of PMA (320 nM), TNF was unable to increase follicular progesterone secretion. The time course of progesterone stimulation by PMA was similar to that of TNF. H-7 also blocked PMA and PMA + TNF stimulated progesterone accumulation, with a 50% inhibition corresponding to 4.2 and 4.1 microM H-7, respectively. These results indicate that PKC may be a mediator of TNF-stimulated progesterone secretion in preovulatory rat follicles.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1975

Differential responses of prelactating and lactating mammary gland to similar tissue concentrations of progesterone.

Serum and mammary tissue concentrations of progesterone and 20alpha-hydroxy-4-pregnen-3-one (20alpha-OHP) were measured by competitive protein-binding assays and gas-liquid chromatography, respectively, in pregnant and lactating rats. The concentration of progesterone in mammary tissue of pregnant rats closely paralleled the serum concentration, particularly when tissue concentration was expressed as ng/mg DNA. The variability in tissue progesterone on the last day of pregnancy was relatively great, but there was a good inverse relation between the appearance of lactose and the progesterone concentration. Serum progesterone levels declined to their lowest values at 1-3 days of lactation (10 plus or minus 1 ng/ml); the tissue concentration declined even more rapidly after parturition. The tissue 20alpha-OHP concentration, which was more closely related to serum progesterone among animals than to serum 20alpha-OHP, remained high after parturition suggesting that the presence of 20alpha-OHP has no effect on lactogenesis and that progesterone is decreased in the tissue by 20alpha-reduction. Following postpartum ovulation, serum progesterone increased to 74 plus or minus 6 ng/ml at 6-9 days of lactation; tissue progesterone also increased to levels found in rats pregnant 14-19 days, yet no change in lactose content of the glands of suckled rats occurred, and the biosynthetic capacity in terms of the RNA/DNA ratio increased. Serum 20alpha-OHP also rose, but the tissue concentration was unchanged, suggesting that saturating levels were present throughout pregnancy and lactation. Since no rapid increase in DNA was associated with lactogenesis, differentiation of nonsecretory parenchymal cells into daughter cells with the secretory capacity must occur earlier in pregnancy. Progesterone, therefore, must inhibit lactogenesis by preventing expression of the genetic potential of daughter cells. Once differentiation has been completed, however, the presence of progesterone in the tissue has no effect on the biosynthesis of milk constituents.

Animals↗
PubMed1996

The extragenomic action of progesterone on human spermatozoa: evidence for a ubiquitous response that is rapidly down-regulated.

Image analysis techniques have been used to demonstrate that progesterone induces a rapid calcium transient in the acrosomal domain of greater than 90% of human spermatozoa (n = 2354). These results are at variance with previous reports, suggesting that progesterone receptors are only expressed on a small subpopulation of these cells, by virtue of their ability to bind fluorescent probes incorporating progesterone 3- (O-carboxymethyl) oxime conjugated to BSA. In the present study, we could confirm that such probes only bound to a small proportion of human spermatozoa (3.01 +/- 0.29%; n = 7557) although 91.79 +/- 1.8% of the same sperm populations exhibited a calcium transient in response to progesterone. These results indicate that the binding of labeled progesterone conjugates to human spermatozoa does not reflect the size of the progesterone responsive population; the response elicited by this steroid is essentially ubiquitous. Progesterone action was shown to involve an influx of extracellular calcium via mechanisms that did not involve voltage sensitive- or second messenger operated-channels, phospholipase C, or G proteins. Despite previous evidence suggesting that progesterone action might involve a GABAA receptor/chloride channel, neither GABA nor the GABA agonist muscimol had any effect on intracellular calcium concentrations in human spermatozoa or influenced their functional competence. The only factor that disrupted the responses of human spermatozoa to progesterone was this steroid itself. Progesterone exposure induced a prolonged period of refractoriness to further stimulation that influenced the capacity of these cells to generate calcium transients, and their ability to exhibit a biological response to changes in intracellular calcium. There are implications in these results for our understanding of the extragenomic action of progesterone on human spermatozoa and the clinical manipulation of this system for the assessment and suppression of human sperm function.

Binding Sites↗
PubMed2006

Dickkopf-1, an inhibitor of Wnt signaling, is regulated by progesterone in human endometrial stromal cells.

CONTEXT: Some members of the Wnt family, including ligands, receptors, inhibitors, and signaling components, are expressed in human endometrium. Dickkopf-1 (Dkk-1), a potent inhibitor of the Wnt signaling pathway, was recently found to be up-regulated in decidualizing endometrial stromal cells during the secretory phase of the menstrual cycle, suggesting regulation by progesterone. OBJECTIVES: To test the hypothesis that progesterone regulates Dkk-1 expression in human endometrial stromal cells, we investigated the following effects on stromal cell expression of Dkk-1 mRNA and protein: decidualizing stimuli (progesterone or cAMP), RU486 (an inhibitor of progesterone action), and withdrawal of progesterone. RESULTS: Short-term treatment (up to 72 h, which corresponds to the full decidualized phenotype in response to cAMP and an early response to progesterone) did not reveal regulation of Dkk-1 mRNA or protein by cAMP but did show induction of Dkk-1 expression when the cells were treated with progesterone, an effect that was blocked by RU486. In long-term cultures (from 14 to 23 d, which corresponds to the full decidualized phenotype in response to progesterone), a significant increase in Dkk-1 mRNA and protein production was observed. Addition of RU486 or withdrawal of progesterone after long-term decidualization resulted in a decrease of Dkk-1 mRNA and protein to control levels. Estradiol alone had no effect on stromal Dkk-1 expression. CONCLUSIONS: These data strongly support regulation by progesterone of Dkk-1 mRNA synthesis and protein expression in human endometrial stromal cells and that the response is specific for progesterone and independent of cAMP and estradiol.

Adult↗
PubMed1993

Progesterone-mediated potentiation of spinal sufentanil in rats.

Pregnancy is associated with an increased sensitivity to both general and local anesthetics. The exact reason is uncertain, but increased concentrations of progesterone and endogenous opiates have been implicated. Therefore, we tested the ability of intrathecally administered progesterone to produce analgesia and to potentiate the effects of spinal sufentanil. Female rats had intrathecal catheters implanted for drug administration, and analgesia was measured using the tail flick assay or hemostat clamp test. Animals were pretreated first with 10 micrograms, 20 micrograms, or 40 micrograms of intrathecal progesterone (n = 5, for each dose) and then given a minimally analgesic dose of sufentanil. Pretreatment with progesterone potentiated sufentanil's effect and resulted in almost complete analgesia. In contrast, in animals not pretreated with progesterone, the same dose of sufentanil resulted in minimal analgesia (n = 15). Intrathecal progesterone alone had no analgesic effects. No behavioral or motor effects were noted after progesterone treatment. Cerebral spinal fluid progesterone levels were within physiologic range. Furthermore, 100 micrograms of progesterone administered intramuscularly did not potentiate sufentanil analgesia. A major progesterone metabolite, 5 alpha-pregnane-3 alpha-ol-20-one, 5 micrograms, 10 micrograms, or 20 micrograms (n = 5, for each dose), also potentiated sufentanil analgesia when administered intrathecally. In contrast, a stereoisomer, 5 beta-pregnane-3 beta-ol-20-one failed to show potentiation. Finally, two drugs that block gamma-aminobutyric acid-mediated increases in chloride ion conductance, picrotoxin and bicuculline, each blocked progesterone-mediated potentiation of sufentanil analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1994

Progesterone stimulates fibronectin production by chicken granulosa cells in vitro.

Experiments were conducted in vitro to examine the effect of progesterone on fibronectin production by chicken ovarian granulosa cells. Granulosa cells isolated from the largest (F1; mature) and third-largest (F3; developing) preovulatory follicles as well as form a pool of immature small yellow follicles (SYF) of the domestic chicken ovary were incubated in serum-free Medium-199 and the amounts of fibronectin and progesterone produced were quantified by enzyme-linked immunosorbent assay and radioimmunoassay respectively. The amounts of basal fibronectin and progesterone produced by granulosa cells from F1, F3 and SYF follicles increased with advancing stages of follicular development. Thus, the quantity of basal fibronectin secreted by granulosa cells was directly proportional to the amount of progesterone produced by them. Exogenously supplied progesterone increased the amount of fibronectin secreted by F1 and F3 cells in a dose-dependent manner, but its effect on SYF cells was marginal. Cyanoketone (an inhibitor of progesterone synthesis) suppressed basal fibronectin production by F1 and F3 granulosa cells and its inhibitory action was reversed by exogenous progesterone. The progesterone antagonist RU 486 also attenuated basal fibronectin production by F1 and F3 granulosa cells, but only the highest concentration affected SYF cells. The inhibitory effect of RU 486 was diminished in the presence of exogenous progesterone. These data show that progesterone regulates fibronectin production by chicken granulosa cells. They suggest that in avian granulosa cells, endogenous progesterone can stimulate fibronectin synthesis in an intracrine or autocrine manner.

Animals↗
PubMed2002

Agonistic and antagonistic properties of progesterone metabolites at the human mineralocorticoid receptor.

OBJECTIVE: Progesterone binds to the human mineralocorticoid receptor (hMR) with nearly the same affinity as do aldosterone and cortisol, but confers only low agonistic activity. It is still unclear how aldosterone can act as a mineralocorticoid in situations with high progesterone concentrations, e.g. pregnancy. One mechanism could be conversion of progesterone to inactive compounds in hMR target tissues. DESIGN: We analyzed the agonist and antagonist activities of 16 progesterone metabolites by their binding characteristics for hMR as well as functional studies assessing transactivation. METHODS: We studied binding affinity using hMR expressed in a T7-coupled rabbit reticulocyte lysate system. We used co-transfection of an hMR expression vector together with a luciferase reporter gene in CV-1 cells to investigate agonistic and antagonistic properties. RESULTS: Progesterone and 11beta-OH-progesterone (11beta-OH-P) showed a slightly higher binding affinity than cortisol, deoxycorticosterone and aldosterone. 20alpha-dihydro(DH)-P, 5alpha-DH-P and 17alpha-OH-P had a 3- to 10-fold lower binding potency. All other progesterone metabolites showed a weak affinity for hMR. 20alpha-DH-P exhibited the strongest agonistic potency among the metabolites tested, reaching 11.5% of aldosterone transactivation. The agonistic activity of 11beta-OH-P, 11alpha-OH-P and 17alpha-OH-P was 9, 5.1 and 4.1% respectively. At a concentration of 100 nmol/l, progesterone, 17alpha-OH-P and 20alpha-DH-P inhibit nearly 75, 40 and 35% of the transactivation by aldosterone respectively. All other progesterone metabolites tested demonstrate weaker affinity, and agonistic and antagonistic potency. CONCLUSIONS: The binding affinity for hMR and the agonistic and antagonistic activity diminish with increasing reduction of the progesterone molecule at C20, C17 and at ring A. We assume that progesterone metabolism to these compounds is a possible protective mechanism for hMR. 17alpha-OH-P is a strong hMR antagonist and could exacerbate mineralocorticoid deficiency in patients with congenital adrenal hyperplasia.

Aldosterone↗
PubMed1986

Acetate and plasma cholesterol as progesterone precursors in the intact ovary of the day-16 pregnant rat.

Rats at Day 16 of pregnancy were infused, via the parametrial artery, with radioactively labelled acetate or cholesterol. All of the venous effluent was collected and examined for radioactive progesterone and related compounds. Labelled progesterone was found in the venous effluent within 15 and 30 min of the start of cholesterol and acetate infusions, respectively, which shows that the ovary can extract both precursors from blood and convert them to progesterone in the intact animal. However, the proportion of secreted progesterone derived from acetate (estimated from labelled progesterone in venous blood) was only 0.21 +/- 0.10% (mean +/- s.e.m.; n = 5). Furthermore, the quantity of labelled progesterone and immediate progesterone precursors remaining in the ovary indicated that less than 0.22 +/- 0.10% of progesterone could have been derived from acetate. In contrast, in rats infused with labelled cholesterol 42 +/- 9% of the progesterone was derived from this source and, from labelled progesterone and immediate precursors of progesterone remaining in the ovary, it was calculated that 53 +/- 10% could have been derived from blood-borne cholesterol.

Acetates↗
PubMed1990

Critical progesterone requirement for maintenance of pregnancy in ovariectomized rats.

The minimum progesterone concentration required to maintain the pregnancy was studied by varying doses of progesterone given subcutaneously to rats ovariectomized on Day 8 of pregnancy. Injecting 3 mg progesterone plus 200 ng oestradiol benzoate daily provided serum progesterone values between 25.4 +/- 7.0 and 35.2 +/- 6.2 ng/ml throughout Days 10-19 which were significantly lower than normal levels (P less than 0.05), but resulted in 93.6% of fetal survival on Day 19 which was not significantly different from 93.3% in the control group. Injecting 2 mg progesterone plus 200 ng oestradiol benzoate daily gave progesterone values between 13.2 +/- 4.6 and 19.0 +/- 6.2 ng/ml and could not maintain fetal viability to Day 19 (14.2%, P less than 0.05 compared with control group). Critical times to supplement progesterone in rats ovariectomized on Day 8 or Day 15 were studied by varying the time of progesterone implantation after ovariectomy. Progesterone implants were administered 8, 12 and 24 h after ovariectomy on Day 8 and 24, 36 and 48 h after ovariectomy on Day 15. On Day 8, progesterone replacement could be delayed to 8 h but not 12 h, while on Day 15, progesterone replacement could be delayed up to 36 h but not 48 h after ovariectomy without affecting fetal survival.

Animals↗