progesterone cream
Effects of progesterone on ovarian tumorigenesis in xenografted mice.

McDonnel AC, Van Kirk EA, Isaak DD, Murdoch WJ.

Departments of Animal Science and Molecular Biology, University of Wyoming, Laramie, WY 82071, USA.

Circumstantial evidence indicates that progestins reduce the risk of epithelial ovarian cancer. We report that the tumorigenic capacity of human ovarian carcinoma (SKOV-3) cells inoculated into the peritoneal cavity of athymic mice is suppressed by pretreatment with subcutaneous progesterone-releasing pellets. Numbers of tumor implants on the intestines/mesentery and invasiveness into underlying host tissues were reduced at 6 weeks following exposure to progesterone. Progesterone prevented tumors from forming on the liver. Life spans of progesterone-treated animals were prolonged. There was no beneficial effect of administration of progesterone if initiated after ovarian tumors had become established on organ surfaces. Our findings implicate a role for progesterone in ovarian cancer prophylaxis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15797626&dopt=Abstract progesterone, progesterone cream



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Actions of progesterone on uterine immunosuppression and endometrial gland development in the uterine gland knockout (UGKO) ewe.

Padua MB, Tekin S, Spencer TE, Hansen PJ.

Department of Animal Sciences, University of Florida, Gainesville, Florida.

In ewes, the uterine gland knockout (UGKO) phenotype is caused by neonatal exposure to norgestomet to arrest uterine gland development and produce an adult which has a uterus characterized by the lack of endometrial glands. Since endometrial glands in the sheep produce the lymphocyte-inhibitory protein, ovine uterine serpin (OvUS), an experiment was conducted with ewes of the UGKO phenotype to evaluate whether the inhibitory actions of progesterone on tissue rejection responses in utero are dependent upon the presence of endometrial glands. Control and UGKO ewes were ovariectomized and subsequently treated with either 100 mg/day progesterone or corn oil vehicle for 30 days. An autograft and allograft of skin were then placed in each uterine lumen and treatments were continued for an additional 30 days before grafts were examined for survival. All autografts survived and had a healthy appearance after histological analysis. Allografts were generally rejected in ewes treated with vehicle but were present for hormone-treated ewes, regardless of uterine phenotype. Analysis of the histoarchitecture and protein synthetic capacity of the uterus revealed that progesterone induced differentiation of endometrial glands and synthesis and secretion of OvUS in UGKO ewes. The UGKO ewes had reduced density of CD45R(+) lymphocytes in the endometrial epithelium and there was a tendency for progesterone to reduce this effect in luminal epithelium. Taken together, results confirm the actions of progesterone to inhibit graft rejection response in utero. Responses of UGKO ewes to progesterone indicate that the hormone can induce de novo development and differentiation of endometrial glands, at least when skin grafts are in the uterus. Mol. Reprod. Dev. (c) 2005 Wiley-Liss, Inc.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15803459&dopt=Abstract progesterone, progesterone cream



progesterone cream
Regulation of the immune response to cestode infection by progesterone is due to its metabolism to estradiol.

Vargas-Villavicencio JA, Larralde C, De Leon-Nava MA, Morales-Montor J.

Departamento de Inmunologia, Instituto de Investigaciones Biomedicas, U.N.A.M., AP 70228, Mexico D.F. 04510, Mexico.

The aim of this work was to investigate the role of progesterone during Taenia crassiceps cysticercosis, and the immunological mechanisms involved in its effects, by relating progesterone treatment to whole parasite counts, to host humoral and cellular immune response, to the presence or absence of nuclear receptors to sex steroids in splenocytes, and to serum sex steroid levels in infected mice of both genders. Progesterone treatment increased parasite loads two-fold in females and three-fold in males compared with control mice. The expression of the Th2 cytokine profile (IL-4, IL-6 and IL-10) was markedly increased in infected mice of both genders, while progesterone treatment returned this expression to basal levels. However, the Th1 cytokine profile (IFN-gamma and TNF-alpha) was not affected by infection, whilst progesterone treatment increased the expression of both cytokines two-fold compared to uninfected, infected and placebo-treated mice. Testosterone serum levels decreased in infected male mice by 95%, and treatment with progesterone did not affect them. In females, no change in testosterone levels was observed. Progesterone levels increased three-fold only in progesterone-treated infected mice of both sexes, while estradiol levels in female and male progesterone-treated infected mice increased two-fold compared to infected control mice. The infection markedly induced the expression of progesterone receptor (PR) isoforms A and B in splenocytes of infected mice of both genders (five-fold). Metabolism of progesterone to estradiol was demonstrated by the use of the anti-estrogen tamoxifen, which reduced parasite loads 100% in infected mice of both sexes treated with progesterone. These results suggest that progesterone, possibly through its metabolism to estradiol, affects establishment, growth and reproduction of the helminth parasite T. crassiceps.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15804489&dopt=Abstract progesterone, progesterone cream



progesterone cream
[Estrogen role in the luteal phase support in in vitro fertilization with embryo transfer cycles]

[Article in Spanish]

Paredes Chavez FC, Barros Delgadillo JC, Ochoa Rueda SS, Barroso Villa G, Villalobos Acosta S, Sanchez Solis V, Osorio Caballero M, Gavino Gavino F.

Servicio de biologia de la reproduccion humana, Instituto Nacional de Perinatologia, Lomas de Chapultepec, Mexico, DF.

OBJECTIVE: To evaluate the effectiveness of estradiol administration for luteal phase support and to describe the progesterone and estradiol behavior in vitro fertilization-embryo transfer luteal phase. MATERIAL AND METHODS: Patients undergoing in vitro fertilization-embryo transfer with controlled ovarian hyperstimulation and using gonadotropin releasing hormone agonist. They were divided at random into two groups: group 1 would receive progesterone alone, and group 2 would take estrogen and progesterone. Serum concentrations of estradiol and progesterone were measured on days 7 and 14 post-embryo transfer. RESULTS: We examined 52 patients; 24 received progesterone alone and 28 took estrogen and progesterone. Significantly higher estradiol and progesterone concentrations on day 14 were found in pregnant women. It was not on day 7. A significant increment of estrogen was found in the estrogen and progesterone group. Progesterone did not increase significantly. Pregnancy rate was the same in both groups. CONCLUSIONS: For patients undergoing in vitro fertilization-embryo transfer, the addition of estradiol to the progesterone support regimen does not have beneficial effects in terms of pregnancy rate. On day 7 neither progesterone nor estradiol are good predictors of pregnancy.

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Actions at GABA(A) receptors in the hippocampus may mediate some antiseizure effects of progestins.

Rhodes ME, Frye CA.

Department of Psychology, University at Albany-SUNY, Albany, NY 12222, USA.

Progestins can have antiseizure effects; however, the mechanisms and sites of action of these effects are not well-understood. Whether progesterone's actions at GABA(A) receptors in the hippocampus are important for its antiseizure effects was investigated. In Experiment 1, ovariectomized rats were administered sesame oil vehicle or a regimen of progesterone (500 microg sc, which produces physiological concentrations in plasma and the hippocampus), followed 2.5 hours later by administration of saline vehicle or a regimen of bicuculline (1 mg/kg, sc), a GABA(A) receptor antagonist, which does not produce any intrinsic effects on seizures. Progesterone, compared with vehicle, significantly increased the latency to, and decreased the number of, pentylenetetrazole-induced tonic seizures and increased GABA-stimulated chloride flux. Co-administration of bicuculline attenuated progesterone's antiseizure effects and decreased GABA-stimulated chloride flux in the hippocampus. Bicuculline did not alter ictal behavior compared with vehicle. In Experiment 2, ovariectomized rats were subcutaneously administered sesame oil or progesterone (500 microg), followed 2.5 hours later by bilateral infusions of bicuculline (100 ng) or vehicle (saline) into the hippocampus. Infusion of bicuculline into the hippocampus of progesterone-primed rats significantly increased ictal activity, compared with that induced by progesterone administration alone, but alone did not alter seizures compared with that produced by saline infusions into the hippocampus. These data suggest that actions of progesterone at GABA(A) receptors in the hippocampus are important for progesterone's antiseizure effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15820338&dopt=Abstract progesterone, progesterone cream



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Progesterone inhibits behavioral responses and estrogen increases corticosterone levels after acute cocaine administration.

Niyomchai T, Russo SJ, Festa ED, Akhavan A, Jenab S, Quinones-Jenab V.

Department of Psychology, Hunter College of the City University of New York and Subprogram in Biopsychology, Graduate School and University Center of the City University of New York, New York, NY 10021, USA.

Accumulating evidence suggests that estrogen and progesterone contribute to the sexually dimorphic behavioral response to cocaine. In this study, we tested the hypothesis that varying the level of estrogen or progesterone affects cocaine-induced locomotive behavior in female rats. Ovariectomized (OVX) rats received estrogen (0, 5, 10, 20, or 50 microg) 48 h or progesterone (0, 50, 100, 250, or 500 microg) 24 h before acute saline or cocaine (15 mg/kg) administration. Although estrogen did not affect cocaine-induced ambulatory and rearing behaviors, it affected stereotypic behaviors regardless of cocaine administration (animals receiving 50 microg had higher stereotypic counts than did the OVX group). In contrast, progesterone affected rearing activity dose-dependently: 50 and 500 microg of progesterone inhibited, whereas 100 microg and 250 microg stimulated, rearing in response to cocaine. That estrogen and progesterone did not affect overall baseline behavioral activity suggests their effects are mediated in part through interactions with cocaine. Progesterone administration did not affect corticosterone levels in saline- or cocaine-treated rats. Estrogen administration, however, affected levels of corticosterone both at baseline and after cocaine treatment. After accounting for baseline differences, we found that rats receiving 5 or 10 microg of estrogen and cocaine had higher percentage increases in serum corticosterone levels than did the control group that did not receive estrogen. On the basis of these observations, we suggest that progesterone fluctuations during the estrous cycle impact cocaine-induced behavioral responses, whereas estrogen may affect activity in the hypothalamic-pituitary-adrenal axis. Thus, dose-dependent effects of gonadal hormones may underlie some of the reported sex differences and reproductive cycle effects of cocaine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15820530&dopt=Abstract progesterone, progesterone cream



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Progesterone synthesis by the human placenta.

Tuckey RC.

Biochemistry and Molecular Biology, School of Biomedical and Chemical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley WA 6009, Australia. rtuckey cyllene.uwa.edu.au

One of the essential roles of the human placenta is to produce the steroid hormone progesterone, which is required for the maintenance of pregnancy. The rate-determining step of placental progesterone synthesis is the conversion of cholesterol to pregnenolone by cytochrome P450scc (CYP11A1) in placental mitochondria in a reaction requiring electrons delivered via adrenodoxin reductase and adrenodoxin. Pregnenolone is converted to progesterone by type 1 3beta-hydroxysteroid dehydrogenase located in the mitochondrion. Progesterone synthesis by the human placenta displays notable differences from steroid synthesis in the classical steroid producing tissues such as the adrenal cortex and corpus luteum. One important difference is that the placenta lacks short term modulation of steroid synthesis and does not express the steroidogenic acute regulatory (StAR) protein. The most notable difference between the placenta and other steroidogenic tissues is that electron supply to P450scc limits the rate at which cholesterol is converted to pregnenolone in the placenta. The limiting component for electron delivery to P450scc is the concentration of adrenodoxin reductase in the mitochondrial matrix which is insufficient to maintain the adrenodoxin pool in a fully reduced state. Evidence suggests that placental mitochondria have a near-saturating cholesterol concentration for P450scc, likely provided by the StAR-like protein MLN64, and cholesterol translocation to the P450scc is not a major site of regulation of progesterone synthesis. Cyclic AMP stimulates progesterone synthesis by the human placenta but uncertainty remains regarding the key hormones that control cyclic AMP levels. The mechanism of regulation of adrenodoxin reductase levels in the human placenta remains to be studied.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15823613&dopt=Abstract progesterone, progesterone cream