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PubMed1996

Endometrial progesterone receptor expression during the human menstrual cycle.

The human endometrium undergoes regular cyclical changes under the endocrine control of oestrogens and progesterone acting via specific nuclear receptors. The molecular and cellular events mediating these changes are not understood. The present study examined the changes in the endometrial progesterone receptor and its mRNA during the menstrual cycle. Forty-four endometrial samples obtained from women with normal menstrual cycles were divided into four categories: early proliferative (days 6-9), late proliferative (days 10-14), early secretory (days 15-21) and late secretory (days 22-28). The progesterone receptor protein was determined using a human progesterone receptor enzyme-linked immunoassay kit. Total RNA was extracted using RNAzol and the abundance of mRNA encoding the progesterone receptor was determined by reverse transcriptase-polymerase chain reaction and by northern blot analysis. The concentration of the progesterone receptor in the endometrium was highest during the late proliferative phase and was lowest in the late secretory phase. Significant differences were observed between the menstrual cycle phases (P < 0.003). No cyclical variation was observed in the concentration of mRNA encoding for the progesterone receptor in the endometrium when analysed by reverse transcriptase polymerase chain reaction or by northern analysis. There appears to be no association between the amounts of mRNA encoding the progesterone receptor and progesterone receptor protein during the menstrual cycle suggesting that the control of the expression of the progesterone receptor may not occur solely at the transcriptional level.

Adult↗
PubMed1990

Synergistic effects of progesterone and oestradiol on rat LH subunit mRNA.

The effects of oestradiol and progesterone on LH-subunit mRNA levels were investigated in ovariectomized rats. Four weeks after ovariectomy, rats were implanted with silicone elastomer capsules containing oestradiol and/or injected daily with progesterone in oil (5 mg/rat) for 8 days. The levels of pituitary mRNA encoding alpha and LH-beta were determined using direct hybridization with specific [32P]cDNA probes. After oestradiol implantation in ovariectomized rats, both alpha and LH-beta mRNA decreased with time, with maximum inhibition after 6-8 days of treatment. Progesterone injected alone did not show any effect on alpha and LH-beta mRNA. Cytosolic progesterone receptors, determined using [3H]methyl-17 alpha-progesterone as ligand, were undetectable in control ovariectomized rats. In contrast, 2 days after oestradiol implantation, the number of receptors increased to 287.5 +/- 35.4 (S.E.M.) fmol/pituitary and reached a plateau of 400 +/- 21.8 fmol/pituitary after 4 days. The effects of progesterone were therefore examined by first implanting ovariectomized rats with oestradiol to induce progesterone receptors and then injecting progesterone daily for a further period of 6 days. As a result of this treatment, progesterone induced a decrease in the pituitary gland contents of both alpha and LH-beta mRNAs, and LH release was significantly greater than that observed in the group receiving oestradiol alone. Moreover, the mRNA levels in the animals treated with oestradiol plus progesterone were lower after 8 days of treatment than those observed in ovariectomized rats treated with a tenfold higher dose of oestradiol alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Dynamics and control of progesterone receptor synthesis in the fetal uterus of the guinea-pig in organ culture.

Progesterone receptor concentrations increased in fetal guinea-pig uterus in organ culture to as high as 13 X 15 +/- 1 X 22 pmol/mg DNA without any added steroid, although cytosol and nuclear oestrogen receptor levels were very low (0 X 41-1 X 92 pmol/mg DNA). Even after a 3-day exposure to 5 X 10(-8) M-progesterone, which inhibits its own receptor (1 X 14 +/- 0 X 31 pmol/mg DNA), progesterone receptor levels rose to 8 X 58 +/- 1 X 39 pmol/mg DNA when progesterone was removed. This replenishment was inhibited by progesterone and 5 alpha-dihydroprogesterone but was not affected by oestradiol, tamoxifen or dexamethasone. The incorporation of [3H]thymidine into nucleic acids was not decreased by progesterone so that its inhibition of its own receptor in the explants was not due to an inhibition of cell replication. Fetal uterine explants from oestrogen-primed fetuses, after an initial decrease in progesterone receptor, also showed a rise to 7 pmol/mg DNA on day 2 which could be decreased by exposure to progesterone and replenished by removal of this hormone (6-8 pmol/mg DNA), the entire process occurring without apparent oestrogen stimulation. Progesterone rather than oestradiol appears to be a key regulator of progesterone receptor synthesis in the fetal guinea-pig uterus, although oestradiol, along with other factors, may also be involved.

Animals↗
PubMed1992

Hormone activation of baculovirus expressed progesterone receptors.

Human and chicken progesterone receptors (A form) were overproduced in a baculovirus expression system. These recombinant progesterone receptors were full-length bound progesterone specifically and were recognized by monoclonal antibodies, AB52 and PR22, specific for human and chicken progesterone receptor, respectively. In gel retardation studies, binding of recombinant human and chicken progesterone receptors to their progesterone response element (PRE) was specific and was enhanced in the presence of progesterone. Binding of human progesterone receptor to the PRE was also enhanced in the presence of the antiprogestin, RU486, but very little effect was observed in the presence of estradiol, dexamethasone, testosterone, and vitamin D. In our cell-free transcription system, human progesterone receptor induced transcription in a receptor-dependent and hormone-activable manner. Receptor-stimulated transcription required the presence of the PRE in the test template and could be specifically inhibited by excess PRE oligonucleotides. Furthermore, chicken progesterone receptor also induced in vitro transcription in a hormone-activable manner. These results demonstrate that steroid receptors overexpressed in a baculovirus expression system are functional and exhibit steroid-responsive binding and transcription. These observations support our present understanding of the mechanism of steroid receptor-regulated gene expression and provide a technological format for studies of the role of hormone and antihormone in altering gene expression.

Animals↗
PubMed1989

Steroid metabolism as a mechanism of escape from progesterone-mediated growth inhibition in Trichophyton mentagrophytes.

It has been shown by us and others that progesterone inhibits the growth of Trichophyton mentagrophytes and that the organism escapes from this inhibition over time. We report here studies which show that escape from growth inhibition is related to the enzymatic transformation of progesterone to polar metabolites. Isolation and identification of the progesterone metabolites confirm the production of 15 alpha-hydroxyprogesterone. In addition, three other metabolites were isolated. Two of these were determined to be 1-dehydroprogesterone and 11 alpha-hydroxyprogesterone. The third metabolite was a 1-dehydro-hydroxyprogesterone, but the location of the hydroxyl group could not be determined unequivocally. Studies using authentic 15 alpha-hydroxyprogesterone, 1-dehydroprogesterone, and 11 alpha-hydroxyprogesterone reveal that these derivatives are significantly less inhibitory to the growth of T. mentagrophytes than progesterone. Pretreatment of organisms with progesterone augments the rate of metabolism and enhances escape. We have described previously a progesterone-binding protein (PBP) in cytoplasmic extracts of T. mentagrophytes and hypothesized that progesterone mediates growth inhibition by binding to the PBP of this organism. The relative binding affinity that progesterone and its metabolites display for PBP correlates with the relative growth inhibitory potency of these compounds. These results suggest that metabolism of progesterone to more polar and less inhibitory compounds, which exhibit lower affinity for PBP, is the mechanism of escape from progesterone-mediated inhibition of growth in this organism.

Binding, Competitive↗
PubMed1981

Sequential inhibition of sexual receptivity by progesterone is prevented by a protein synthesis inhibitor and is not causally related to decreased levels of hypothalamic progestin receptors in the female rat.

In the estrogen-primed ovariectomized female rat, the administration of progesterone facilitates sexual receptivity and activates proceptivity for many hours. If the progesterone dose is large (e.g., 2.5 mg), a refractory period follows, during which time animals are less sensitive to additional progesterone. This refractory period has been termed "sequential inhibition" and has been correlated previously with decreased levels of cytosol progestin receptors in the mediobasal hypothalamus-preoptic area (MBH-POA). Our present results indicate that the "sequential inhibition" of mating behavior by progesterone appears to involve a protein synthetic step that is not related causally to decreased levels of cytosol progestin receptors in the MBH-POA. Animals which received subcutaneous injections of the protein synthesis inhibitor, anisomycin (100 mg/kg in saline), 15 min prior to and again 3 hr after progesterone (2.5 mg in propylene glycol) treatment, displayed greater sexual receptivity at 24 hr than did animals which received subcutaneous saline injections. However, cytosol progestin receptor levels in the MBH-POA of animals which received anisomycin plus progesterone were decreased at 24 hr, relative to animals which received saline plus progesterone. Anisomycin did not produce positive or negative behavioral effects at 24 hr when administered 15 min prior to and again 3 hr after propylene glycol, suggesting that the behavioral effects of anisomycin appear to be related to selective blockade of progesterone action. In separate experiments, we administered single subcutaneous injections of anisomycin at various times relative to progesterone (2.5 mg) treatment. According to the time course of effective anisomycin application, the presumed protein synthesis which is responsible for the inhibition of mating behavior occurs between 3 and 13 hr after the administration of progesterone.

Animals↗
PubMed1977

Sustained-release hormonal preparations XV: release of progesterone from cholesterol pellets in vivo.

Progesterone-sterol pellets were made that porvided a zero-order release of progesterone for 80 days. 4-(14)C-Progesterone was used to measure the release in vitro and in vivo. The dissolution rate in vitro (distilled water as the desorbing medium) for progesterone-cholesterol (59:41 w/w) and the progesterone-beta-sitosterol (47:53 w/w) pellets was 72 microng/100 mm2/24 hr. The average in vivo absorption from subcutaneously implanted pellets in rabbits was 2 +/- 0.1 microng/ml of plasma/cm2 of surface area. Of this amount, 20-25% was progesterone; the remainder was progesterone metabolites and conjugates. Zero-order release (plasma levels) was obtained for approximately 80 days or until about 70% of the available progesterone was exhausted. During this time, the level of excreted radioactivity in urine continuously decreased, indicating that monitoring only this parameter would lead to erroneous conclusions. A long-term effect and increased effectiveness were obtained with a 5-20-mg progesterone equivalent dose, using gel prepared from 2% methylcellulose as the suspending medium.

Animals↗
PubMed1996

Progesterone triggers rapid transmembrane calcium influx and/or calcium mobilization from endoplasmic reticulum, via a pertussis-insensitive G-protein in granulosa cells in relation to luteinization process.

We investigated the early effects (5-60 s) of progesterone (1 pM-0.1 microM) on cytosolic free calcium concentration ([Ca2+]i) and inositol 1,4,5-trisphosphate (InsP3) formation in nonluteinized and in vitro luteinized porcine granulosa cells (pGCs). Progesterone increased [Ca2+]i and InsP3 formation within 5 s in both cell types. Progesterone induced calcium mobilization from the endoplasmic reticulum via the activation of a phospholipase C linked to a pertussis-insensitive G-protein. This process was controlled by protein kinases C and A. In contrast, only nonluteinized pGCs showed a Ca2+ influx via dihydropyridine-insensitive calcium channel. In both cell types, the nuclear progesterone receptor antagonist RU-38486 did not inhibit the progesterone-induced increase in [Ca2+]i, progesterone immobilized on bovine serum albumin, which did not enter the cell, increased [Ca2+]i within 5 s and was a full agonist, but less potent than the free progesterone; pertussis toxin did not inhibit progesterone effect on InsP3. In conclusion, progesterone may interact with membrane unconventional receptors that belong to the class of membrane receptors coupled to a phospholipase C via a pertussis toxin-insensitive G-protein. The source of the Ca2+ for the progesterone-induced increase in [Ca2+]i also depends on the stage of cell luteinization.

Animals↗
PubMed2000

Estradiol and progesterone regulate the expression of insulin-like growth factor-I receptor and insulin-like growth factor binding protein-2 in the hypothalamus of adult female rats.

Gonadal hormones interact with insulin-like growthfactor-I (IGF-I) to regulate synaptic plasticity during the estrous cycle in the rat mediobasal hypothalamus. It has been proposed that tanycytes, specialized glial cells lining the ventral region of the third ventricle, may regulate the availability of IGF-I to hypothalamic neurons. IGF-I levels in tanycytes fluctuate during the estrous cycle. Furthermore, estrogen administration to ovariectomized rats increases IGF-I levels in tanycytes, while progesterone, injected simultaneously with estrogen, blocks the estrogen-induced increase of IGF-I levels in tanycytes. To test whether hormonal regulation of IGF-I receptor (IGF-IR) and IGF binding protein-2 (IGFBP-2) may be involved in the accumulation of IGF-I in tanycytes, we assessed the effect of ovarian hormones on the levels of these molecules in the mediobasal hypothalamus of adult female rats. Ovariectomized animals were treated with either oil, estrogen, progesterone, or estrogen and progesterone simultaneously and then killed 6 or 24 h later. Some neurons, some astrocytes, and many tanycytes in the mediobasal hypothalamus were found by confocal microscopy to be immunoreactive for IGF-IR. IGFBP-2 immunoreactivity was restricted almost exclusively to tanycytes and ependymal cells and was colocalized with IGF-IR immunoreactivity in tanycytes. By electron microscope immunocytochemistry using colloidal gold labeling, IGF-IR and IGFBP-2 immunoreactivities were observed in the microvilli of tanycytes in the lumen of the third ventricle. IGF-IR and IGFBP-2 immunoreactive levels on the apical surface of tanycytes were significantly decreased by the administration of progesterone, either alone or in the presence of estradiol. IGF-IR levels in the mediobasal hypothalamus, measured by Western blotting, were not significantly affected by the separate administration of estradiol or progesterone to ovariectomized rats. However, the simultaneous administration of both hormones resulted in a marked decrease in IGF-IR protein levels. Estradiol administration to ovariectomized rats increased IGFBP-2 immunoreactive levels in the hypothalamus. While progesterone did not significantly affect IGFBP-2 expression, the simultaneous injection of estradiol and progesterone resulted in a marked decrease in IGFBP-2 protein levels. The effect of estradiol on IGFBP-2 was observed both in protein and mRNA levels, suggesting a transcriptional regulation. However, the simultaneous administration of progesterone and estradiol had different effects on IGF-IR protein and IGF-IR mRNA levels, as well as on IGFBP-2 protein and IGFBP-2 mRNA levels, suggesting a postranscriptional action. These findings indicate that estradiol and progesterone regulate the expression of IGF-IR and IGFBP-2 in the mediobasal hypothalamus of adult female rats. Regulation of the hypothalamic IGF-I system by ovarian hormones may be physiologically relevant for neuroendocrine regulation and for synaptic plasticity during the estrous cycle. These results do not support the hypothesis that estrogen-induced accumulation of IGF-I by tanycytes is mediated by the hormonal regulation of IGF-IR. However, estrogen-induced up-regulation of IGFBP-2 and progesterone-induced down-regulation of IGF-IR and IGFBP-2 levels in the apical plasma membrane of tanycytes may be involved in the fluctuation of IGF-I levels in the mediobasal hypothalamus during the estrous cycle.

Age Factors↗
PubMed2005

Progesterone primes zona pellucida-induced activation of phospholipase A2 during acrosomal exocytosis in guinea pig spermatozoa.

We investigated, using guinea-pig spermatozoa as a model, whether phospholipase A2 (PLA2) is involved in progesterone or zona pellucida (ZP)-stimulated acrosomal exocytosis, if progesterone enhances ZP-induced activation of PLA2, and mechanisms underlying PLA2 regulation. Spermatozoa were capacitated and labeled in low Ca2+ medium with [14C]choline chloride or [14C]arachidonic acid, washed, and then exposed to millimolar Ca2+ and progesterone and/or ZP. Each agonist stimulated decrease of phosphatidylcholine (PC) and release of arachidonic acid and lysoPC, indicative of PLA2 activation. Aristolochic acid (a PLA2 inhibitor) abrogated lipid changes and exocytosis, indicating that these lipid changes are essential for exocytosis. Exposure of spermatozoa to submaximal concentrations of both progesterone and ZP resulted in a synergistic increase of arachidonic acid and lysoPC releases, and exocytosis, suggesting that, under natural conditions, both agonists interact to bring about acrosomal exocytosis. Progesterone-induced PLA2 activation appears to be mediated by a GABA(A)-like receptor, because bicuculline (a GABA(A) receptor antagonist) blocked arachidonic acid release and exocytosis. In agreement with this, GABA mimicked progesterone actions. ZP-induced activation of PLA2 seemed to be transduced via G(i) proteins because pertussis toxin blocked arachidonic acid release and acrosomal exocytosis. PLA2 may be regulated by PKC because progesterone- or ZP-induced release of arachidonic acid was blocked by the PKC inhibitors staurosporine or chelerythrine chloride. PLA2 could also be regulated by the cAMP-PKA pathway; inclusion of the PKA inhibitor 14-22 amide or H-89 led to a reduction in arachidonic acid release or exocytosis after progesterone or ZP. Taken together, these results suggest that PLA2 plays an essential role in progesterone or ZP-stimulated exocytosis with progesterone priming ZP action.

Acrosome↗
PubMed1983

In vitro estrogen modulation of pituitary and progesterone-induced oocyte maturation in Rana pipiens.

The role of estrogen in the process of hormone-induced meiotic maturation was investigated using in vitro culture of Rana pipiens ovarian follicles and isolated oocytes. Estrogen alone was ineffective in triggering maturation and did not act synergistically when combined with progesterone. Instead, slight inhibitory effects on oocyte maturation were observed when estrogen was added to the culture medium simultaneously with progesterone. Prolonged estrogen pretreatment (1-8 hr) was seen to be increasingly effective in inhibiting progesterone-induced germinal vesicle breakdown (GVBD). Washing follicles after estrogen pretreatment diminished the inhibitory effects, suggesting continued presence of estrogen was necessary for maximal inhibition. Progesterone-induced GVBD was inhibited by estrogen in denuded oocytes (follicle wall removed) indicating that estrogen acts directly on the oocyte. Incorporation of radioactive progesterone into ovarian follicles was not inhibited regardless of the estrogen concentration used. This suggests that estrogen inhibits oocyte maturation by raising intrafollicular threshold to progesterone rather than by suppressing hormone incorporation into ovarian follicles. Next, the action of estrogen on frog pituitary homogenate (FPH)-induced GVBD was examined although both progesterone and FPH-induced GVBD were inhibited by estrogen, the latter was remarkably more susceptible and did not require estrogen pretreatment. Furthermore, increased concentration of progesterone, but not FPH, overcame the inhibitory action of estrogen. The results suggest that estrogen may exert its inhibitory effects on gonadotropin action at more than one site. Estrogen can modulate either the maturation-inducing action of progesterone directly at the oocyte level or the suppression of progesterone production by the follicle cell. Hence, estrogen may play an important role as an endogenous regulator of oocyte meiotic maturation.

Animals↗
PubMed2006

Reduced metabolites mediate neuroprotective effects of progesterone in the adult rat hippocampus. The synthetic progestin medroxyprogesterone acetate (Provera) is not neuroprotective.

The ovarian hormone progesterone is neuroprotective in different experimental models of neurodegeneration. In the nervous system, progesterone is metabolized to 5alpha-dihydroprogesterone (DHP) by the enzyme 5alpha-reductase. DHP is subsequently reduced to 3alpha,5alpha-tetrahydroprogesterone (THP) by a reversible reaction catalyzed by the enzyme 3alpha-hydroxysteroid dehydrogenase. In this study we have analyzed whether progesterone metabolism is involved in the neuroprotective effect of the hormone in the hilus of the hippocampus of ovariectomized rats injected with kainic acid, an experimental model of excitotoxic cell death. Progesterone increased the levels of DHP and THP in plasma and hippocampus and prevented kainic-acid-induced neuronal loss. In contrast to progesterone, the synthetic progestin medroxyprogesterone acetate (MPA, Provera) did not increase DHP and THP levels and did not prevent kainic-acid-induced neuronal loss. The administration of the 5alpha-reductase inhibitor finasteride prevented the increase in the levels of DHP and THP in plasma and hippocampus as a result of progesterone administration and abolished the neuroprotective effect of progesterone. Both DHP and THP were neuroprotective against kainic acid. However, the administration of indomethacin, a 3alpha-hydroxysteroid dehydrogenase inhibitor, blocked the neuroprotective effect of both DHP and THP, suggesting that both metabolites are necessary for the neuroprotective effect of progesterone. In conclusion, our findings indicate that progesterone is neuroprotective against kainic acid excitotoxicity in vivo while the synthetic progestin MPA is not and suggest that progesterone metabolism to its reduced derivatives DHP and THP is necessary for the neuroprotective effect of the hormone.

3-Hydroxysteroid Dehydrogenases↗
PubMed2000

Sandwich configuration of type I collagen suppresses progesterone production in primary cultured porcine granulosa cells by reducing gene expression of cytochrome P450 cholesterol side-chain cleavage enzyme.

When porcine granulosa cells were cultured on type I collagen (TIC)-coated dishes, progesterone was continuously secreted in the culture medium. However, when cells were overlaid with a TIC gel, progesterone production was decreased to 34% (day 3) and 16% (day 4) of the value measured for cells without the overlay. The effect of TIC gel overlay on cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), which catalyzes the conversion of cholesterol to pregnenolone and is thought to be the rate-limiting enzyme in the conversion of cholesterol to progesterone, was examined. P450scc gene expression in cells overlaid with a TIC gel was decreased to 62% (day 3) and 36% (day 4) of the value measured for cells without the overlay. Amounts of P450scc were also reduced in the cells overlaid with a TIC gel. When pregnenolone, the direct precursor of progesterone, was added to the culture medium, the increase in progesterone production by cells overlaid with a TIC gel was much greater than that for cells without a TIC gel and a statistical difference in progesterone production was no longer observed between the two groups of cells. Treatment of the cells with human FSH (hFSH) enhanced progesterone production in a dose-dependent manner, irrespective of the presence of a TIC gel overlay. Moreover, hFSH induced P450scc gene expression in cells with and without a TIC gel overlay. These results indicate that a TIC gel overlay reduces progesterone production in granulosa cells via the suppression of P450scc gene expression. This supports the possibility that the existence of a TIC gel on the apical side of granulosa cells prevents the spontaneous luteinization of granulosa cells cultured on TIC-coated dishes. The fact that hFSH overcomes the suppressive effect of the TIC gel overlay on progesterone production may explain the mechanism for the subtle rise in serum progesterone concentration in the late follicle phase of the "in vitro fertilization" program.

Animals↗
PubMed1997

Changes in plasma concentrations of luteinizing hormone, progesterone, and testosterone in turkey hens during the ovulatory cycle.

Changes in luteinizing hormone (LH), progesterone, and testosterone concentrations were determined in blood samples taken every 10 min for 26 hr during an ovulatory cycle in laying turkey hens. During the 26-hr sampling period, one peak of both LH and progesterone and numerous peaks of testosterone were detected. The concentration of LH in plasma increased from basal level (2.44-4.0 ng/ml) to maximum level (8.57-24.3 ng/ml) over 1 to 2 hr and then declined over 3 to 5 hr to a basal level. The duration of the descending portion of the peak was about double that of the ascending portion. The concentration of progesterone increased rapidly from a basal level of 1.18-1.65 ng/ml to a peak of 6.18-11.87 ng/ml and then maintained a plateau before rapidly declining to basal level. The concentration of testosterone increased from a basal level of 0.06-0.09 ng/ml to a peak level of 0.13-0.30 ng/ml. All maximum levels of testosterone preceded those of LH, and all maximum levels of LH preceded those of progesterone. The durations of the progesterone peaks were longer than those of the LH peaks. Progesterone concentrations returned to basal level after LH had returned to basal level, although the initial increase in progesterone concentration was earlier, later, or at the same time as LH. Peak durations of testosterone were variable. The preovulatory surges of LH and progesterone of five of nine sets of samples started at the end of the scotophase and ended during the beginning portion of the photophase. In three of nine sets both the start and the end occurred druing the scotophase and in one of nine sets during the photophase. It was concluded from this study that the patterns of secretion of LH, progesterone, and testosterone were similar in that the preovulatory surge was superimposed on a relatively stable basal level, while the temporal relationships of the ovulatory surges of these hormones were variable. The preovulatory surges were more tightly associated with ovulation rather than with photoperiod. Neither progesterone nor testosterone might be an initiator of the LH surge prior to ovulation.

Animals↗
PubMed2001

Estrogen-inducible progesterone receptors in the rat lumbar spinal cord: regulation by ovarian steroids and fluctuation across the estrous cycle.

Ovarian hormones influence the physiology of the spinal cord through incompletely understood cellular mechanisms. To date, there has been little compelling evidence for progesterone receptors in spinal cord neurons. Using two antibodies specific for progesterone receptors in an immunohistochemical investigation, we now report the presence of estrogen-inducible progesterone receptors in the spinal cord. Estrogen-inducible progesterone receptors were observed in the neurons of lamina X and the interomedialateral cell column, which are also known to express estrogen receptors. Estrogen-inducible progesterone receptors similar to those observed in females were also apparent in lamina X and interomediolateral cell column neurons in the spinal cords of males treated with estradiol. Furthermore, the density of progesterone receptors in lamina X was observed to fluctuate across the estrous cycle in female rats, with the highest progesterone receptor expression levels occurring late in proestrus, following the estradiol surge and coincident with high circulating progesterone levels. The lowest progesterone receptor expression levels were observed late in estrus following the progesterone surge. Together, these results demonstrate that estrogen-sensitive progestin targets exist in the spinal cord, and their possible role in the nervous control of reproduction and ovarian steroid modulation of nociception is discussed.

Animals↗
PubMed1993

Effect of progesterone pretreatment on cadmium toxicity in the male Fischer (F344/NCr) rat.

A previous report has indicated that progesterone pretreatment can markedly reduce cadmium toxicity in male NAW mice. Therefore we examined the effects of progesterone pretreatment on cadmium toxicity in male Fischer (F344/NCr) rats. A single sc injection of 20 mumol CdCl2/kg proved nonlethal over 24 hr but caused the typical spectrum of testicular lesions in these rats. However, when rats were pretreated with progesterone (100 mg/kg, sc, -48, -24, and 0 hr) and then given cadmium (20 mumol CdCl2/kg, 0 hr), this dose of cadmium proved very toxic, unexpectedly causing a 53% mortality. Progesterone pretreatment had no effect on cadmium-induced testicular lesions in surviving rats. Significant elevations in serum lactate dehydrogenase (LDH) activity, indicative of hepatotoxicity, were also observed in progesterone-pretreated rats given cadmium as compared to rats given cadmium alone. Progesterone pretreatment had no effect on the distribution of cadmium to liver, kidney, or testes. Progesterone pretreatment also had no effect on the cadmium-induced increases in hepatic or renal metallothionein (MT) or hepatic or testicular MT mRNA levels. In contrast, levels of the testicular cadmium-binding protein (TCBP) in progesterone-pretreated rats were doubled. These results indicate that, contrary to previously reported data for the mouse, progesterone pretreatment increased the lethality of cadmium in male Fischer (F344/NCr) rats and had no effect on cadmium-induced testicular toxicity. The mechanism by which progesterone enhanced cadmium toxicity, especially cadmium-induced hepatotoxicity, deserves further study.

Animals↗
PubMed1994

Serum progesterone concentrations on the day after human chorionic gonadotropin administration and progesterone/oocyte ratios predict in vitro fertilization/embryo transfer outcome.

PURPOSE: In gonadotropin-releasing hormone analogue-pretreated in vitro fertilization-embryo transfer cycles, pregnancy rates are inversely related to serum progesterone levels on the day of administration of human chorionic gonadotropin. The relationship of the progesterone concentration on other days in the periovulatory period to pregnancy rates in such cycles is little studied. We therefore retrospectively analyzed the relationship between progesterone concentrations on the day after human chorionic gonadotropin and pregnancy in 114 cycles, 28 and 23 of which produced clinical and ongoing/delivered pregnancies, respectively. To assess the effect of the extent of follicular luteinization on success, we also studied the relationship between the progesterone concentration per oocyte retrieved and pregnancy for the day of and day after human chorionic gonadotropin. RESULTS: Progesterone concentrations on the day after human chorionic gonadotropin were inversely associated with clinical pregnancy by multiple logistic regression analysis (P < 0.05). Progesterone/oocyte ratios were inversely associated with clinical pregnancy (P < 0.05) and ongoing/delivered pregnancy (P < 0.02) for both the day of and the day after human chorionic gonadotropin. CONCLUSION: The study results extend the window of time during which elevated progesterone concentration is associated with poor outcome to at least 2 days. This finding is consistent with hypothetical mechanisms attributing the link between progesterone concentration and outcome to either endometrial or follicle/oocyte events. The association of lack of follicular luteinization (low progesterone per oocyte ratios) and favorable outcome suggests a predominant effect of progesterone on follicle/oocyte quality. Further studies are needed to clarify the mechanisms underlying the association between progesterone and in vitro fertilization-embryo transfer outcome.

Adult↗
PubMed1997

Progesterone protects against lipid peroxidation following traumatic brain injury in rats.

The gonadal hormone, progesterone, has been shown to have neuroprotective effects in injured nervous system, including the severity of postinjury cerebral edema. Progesterone's attenuation of edema is accompanied by a sparing of neurons from secondary neuronal death and with improvements in cognitive outcome. In addition, we recently reported that postinjury blood-brain barrier (BBB) leakage, as measured by albumin immunostaining, was significantly lower in progesterone treated than in nontreated rats, supporting a possible protective action of progesterone on the BBB. Because lipid membrane peroxidation is a major contributor to BBB breakdown, we hypothesized that progesterone limits this free radical-induced damage. An antioxidant action, neuroprotective in itself, would also account for progesterone's effects on the BBB, edema, and cell survival after traumatic brain injury. To test progesterone's possible antiperoxidation effect, we compared brain levels of 8-isoprostaglandin F2 alpha (8-isoPGF2 alpha), a marker of lipid peroxidation, 24, 48, and 72 h after cortical contusion in male rats treated with either progesterone or the oil vehicle. The brains of progesterone treated rats contained approximately one-third of the 8-isoPGF2 alpha found in oil-treated rats. These data suggest progesterone has antioxidant effects and support its potential as a treatment for brain injury.

Animals↗