progesterone cream
Transcription-dependent and transcription-independent functions of the classical progesterone receptor in Xenopus ovaries.

Liu XS, Ma C, Hamam AW, Liu XJ.

Ottawa Health Research Institute, Ottawa Hospital Civic Campus, 1053 Carling Avenue, Ottawa, Ontario, Canada K1Y 4E9; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada.

Two forms of the classical progesterone receptors (PR), XPR-1 and XPR-2, have been cloned in Xenopus laevis. Their relative roles in mediating progesterone action in the ovaries are not clear. Using antibodies generated against the cloned XPR-2, we demonstrated here that the somatic follicle cells expressed an 80-kDa PR protein, termed XPR-1. Treatment of follicle cells with progesterone resulted in disappearance of this protein, consistent with proteosome-mediated XPR-1 protein degradation. A smaller ( approximately 70 kDa) PR protein, termed XPR-2, was expressed in the oocytes, but not in follicle cells. XPR-2 underwent progesterone-induced phosphorylation but not protein degradation. Treating isolated ovarian fragments with progesterone caused oocyte maturation and the release of the mature oocytes from the ovarian tissues ("ovulation"). Inhibition of transcription, with actinomycin D, did not interfere with progesterone-induced oocyte maturation but blocked "ovulation" so that mature oocytes were trapped in the follicles. These results suggest that the dual functions of progesterone, transcription-dependent follicle rupture and transcription-independent oocyte maturation, are mediated by the two forms of PR proteins differentially expressed in the follicle cells and the oocytes, respectively.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15890333&dopt=Abstract progesterone, progesterone cream



progesterone cream
Altered profiles of serum neuroactive steroids in premenopausal women treated for alcohol addiction.

Hill M, Popov P, Havlikova H, Kancheva L, Vrbikova J, Kancheva R, Pouzar V, Cerny I, Starka L.

Institute of Endocrinology, Narodni Trida 8, CZ 11694 Prague 1, Czech Republic.

Long-term alcohol consumption results in menstrual irregularities due to the inhibition of progesterone secretion. Some progesterone metabolites, including three pregnanolone isomers (PI), abate, while pregnenolone sulfate (PregS) and dehydroepiandrosterone sulfate (DHEAS) increase, alcohol tolerance. The rationale of this study was to evaluate how the neuroactive steroids reflect the impaired progesterone formation in premenopausal women treated for alcohol addiction, and whether detoxification therapy could restore female reproductive functions and psychosomatic stability by reinstatement of the steroid biosynthesis. Accordingly, serum allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one (P3alpha5alpha)), pregnanolone (P3alpha5beta), isopregnanolone (P3beta5alpha) and epipregnanolone (P3beta5beta), progesterone, PregS, pregnenolone, 17alpha-hydroxy-pregnenolone (Preg17), 17alpha-hydroxy-progesterone (Prog17), DHEA, DHEAS, cortisol and estradiol were measured in 20 women during the therapy (start, 3 days, 14 days, 1 month, 4 months), and in 17 controls, using GC-MS or RIA and evaluated by age-adjusted ANCOVA with status and phase of the menstrual cycle (PMC) as factors, and status-PMC interaction. The patients exhibited depressed progesterone, Prog17, PI, and estradiol, a decreased progesterone/pregnenolone ratio, a decreased ratio of neuroinhibiting P3alpha5alpha to neuroactivating PregS, and an elevated PregS and PregS/pregnenolone ratio. The treatment mostly restored the indices. The reduction of neuroinhibiting pregnanolone isomers in the patients is primarily associated with the impairment in ovarian steroid biosynthesis. Nevertheless, changes in enzyme activities connected with the formation of PI and the influence of altered physiological requirements on the balance between endogenous neuroinhibiting and neuroactivating steroids are also likely. The reinstatement of serum estradiol, progesterone, and PI during the therapy demonstrates its favorable effect on both reproductive functions and the psychosomatic stability of the patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15894035&dopt=Abstract progesterone, progesterone cream



progesterone cream
The effects of the neurosteroids: pregnenolone, progesterone and dehydroepiandrosterone on muscarinic receptor-induced responses in Xenopus oocytes expressing M1 and M3 receptors.

Horishita T, Minami K, Uezono Y, Shiraishi M, Ogata J, Okamoto T, Terada T, Sata T.

Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu, 807-8555, Japan, kminami med.uoeh-u.ac.jp.

The neurosteroids pregnenolone, progesterone, and dehydroepiandrosterone (DHEA) occur naturally in the nervous system. They act on neural tissues, participate in neuronal signaling, and are reported to alter neuronal excitability via nongenomic mechanisms. Muscarinic receptors have important roles in neuronal functions in the brain and autonomic nervous system. In this study, we investigated the effects of pregnenolone, progesterone, and DHEA on M(1) and M(3) muscarinic receptors using the Xenopus oocyte expression system. Pregnenolone and progesterone inhibited the acetylcholine (ACh)-mediated responses of M(1) and M(3) receptors expressed in Xenopus oocytes, whereas DHEA did not. The half-maximal inhibitory concentrations (IC(50)) for pregnenolone inhibition of M(1) receptor- and M(3) receptor-mediated currents were 11.4 and 6.0 muM respectively; the IC(50) values for progesterone inhibition of M(1) receptor- and M(3) receptor-mediated currents were 2.5 and 3.0 muM respectively. The selective protein kinase C (PKC) inhibitor GF109203X had little effect on the pregnenolone or progesterone inhibition of the ACh-induced currents in Xenopus oocytes expressing M(1) or M(3) receptors. The inhibitory effects of pregnenolone and progesterone were overcome at higher concentrations of ACh. Pregnenolone and progesterone inhibited the [(3)H]quinuclidinyl benzilate (QNB) binding to M(1) and M(3) receptor expressed in Xenopus oocytes, and Scatchard plot analysis of [(3)H]QNB binding revealed that pregnenolone and progesterone altered the K(d) value and the B(max), indicating noncompetitive inhibition. In conclusion, pregnenolone and progesterone inhibited M(1) and M(3) receptor functions noncompetitively by the mechanism independent of PKC and by interfering with ACh binding to the receptors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15900516&dopt=Abstract progesterone, progesterone cream



progesterone cream
Progesterone supplementation for preventing preterm birth: a systematic review and meta-analysis.

Dodd JM, Crowther CA, Cincotta R, Flenady V, Robinson JS.

Department of Obstetrics and Gynaecology, The University of Adelaide, Adelaide, Australia.

Aim. The aim of this study is to assess the role of progesterone in preterm birth prevention. Methods. A MEDLINE search (from 1966 to the present; date of last search January 2005) was performed - using the key words progesterone, pregnancy, preterm birth, preterm labor, and randomized, controlled trial - in order to identify randomized, controlled trials in which progesterone (either intramuscular or vaginal administration) was compared with placebo or no treatment. Data were extracted and a meta-analysis was performed. Results. Seven randomized, controlled trials were identified. Women who received progesterone were statistically significantly less likely to give birth before 37 weeks (seven studies, 1020 women, RR = 0.58, 95% CI = 0.48-0.70), to have an infant with birth weight of </=2.5 kg (six studies, 872 infants, RR = 0.62, 95% CI = 0.49-0.78), or to have an infant diagnosed with intraventricular hemorrhage (one study, 458 infants, RR = 0.25, 95% CI = 0.08-0.82). Conclusions. For progesterone supplementation to be advocated for women at the risk of preterm birth, the prolongation of gestation demonstrated in this meta-analysis must translate into improved infant outcomes, including a reduction in mortality. There is currently insufficient information to allow recommendations regarding the optimal dose, route, and timing of administration of progesterone supplementation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15901258&dopt=Abstract progesterone, progesterone cream



progesterone cream
Over-the-Counter Progesterone Cream Produces Significant Drug Exposure Compared to a Food and Drug Administration-Approved Oral Progesterone Product.

Hermann AC, Nafziger AN, Victory J, Kulawy R, Rocci ML Jr, Bertino JS Jr.

Jr, PharmD, Ordway Clinical Research, 150 New Scotland Avenue, Albany, NY 12208.

Progesterone products are available in prescription form as well as over-the-counter (OTC) topical preparations sold for "cosmetic" uses. In a randomized study design, the authors compared the drug exposure from an OTC progesterone cream to a Food and Drug Administration-approved oral preparation at the labeled daily doses recommended for each product. Twelve healthy postmenopausal women received 200-mg oral progesterone capsules once daily for 12 days or progesterone cream 40 mg twice daily for 12 days. At steady state (day 12 of each phase), whole-blood samples were collected over 24 hours (oral progesterone) or 12 hours (topical progesterone) and assayed for total progesterone concentration. No significant differences were found in dose-normalized 24-hour progesterone exposure comparing the cream to oral capsules (median AUC(0-24) 12.5 ng.h/mL vs 10.5 ng.h/mL, respectively; P = .81). In light of the potential risks associated with long-term progesterone use, the authors question whether topical progesterone products should be available OTC.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15901742&dopt=Abstract progesterone, progesterone cream



progesterone cream
Vaginal ring delivering estradiol and progesterone: a possible alternative to relieve climacteric symptoms.

Ben-Chetrit A, Hochner-Celnikier D, Lindenberg T, Zacut D, Shimonovitz S, Gelber H, Spitz IM.

Women's Health Center (Ramat Eshkol), Shaare Zedek Medical Center, Jerusalem. benchet 012.net.il

BACKGROUND: Relief of climacteric symptoms is currently the main role of hormone therapy. However, vaginal bleeding complicating this therapy is among the leading causes for its early discontinuation. OBJECTIVES: To assess the effect of a vaginal ring delivering estradiol and progesterone in postmenopausal women and to determine whether continuous administration can relieve climacteric symptoms, produce an acceptable pattern of vaginal bleeding and control endometrial proliferation. METHODS: Twenty-nine postmenopausal women with an intact uterus were studied. All had climacteric symptoms. The vaginal rings contained 0.36 g estradiol and either 3.6 g progesterone (high dose progesterone) or 1.8 g (low dose progesterone), and were kept in place for 4-6 months. Serum progesterone, estradiol and estrone were measured and endometrial thickness determined. All women kept a daily diary of bleeding/spotting and completed a questionnaire on climacteric symptoms at monthly intervals. The low dose progesterone group comprised 14 women and the high dose progesterone group 15 women. RESULTS: A total of 18 patients (9 in each group) completed the study. Mean levels of estradiol, estrone and progesterone were at their peak after 2 to 4 weeks. All rings were effective in alleviating vasomotor symptoms, although there was evidence of "escape from effect" in month 6. Endometrial thickness increased in 6 of the 29 women but biopsy in each case showed no evidence of hyperplasia. Of the 18 women who completed the study, 5 had amenorrhea throughout, 7 had amenorrhea after 3 months, and the remainder had one or two bleeding episodes after 3 months. Therapy was discontinued in 11 women. CONCLUSIONS: A vaginal ring delivering estradiol and progesterone controlled climacteric symptoms, prevented endometrial proliferation, and provided an acceptable bleeding pattern. It should be viewed as a possible alternative for short-term estrogen-progesterone therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15909462&dopt=Abstract progesterone, progesterone cream



progesterone cream
Sexually dimorphic hormonal regulation of the gap junction protein, CX43, in rats and altered female reproductive function in CX43+/- mice.

Gulinello M, Etgen AM.

Albert Einstein College of Medicine, Department of Neuroscience, 1300 Morris Park Avenue F113, Bronx, NY 10461, USA.

Astrocytic gap junctional communication is important in steroid hormone regulation of reproductive processes at the level of the hypothalamus, including estrous cyclicity and sexual behavior. We examined the effects of estradiol and progesterone on the abundance of the gap junctional protein, connexin 43 (CX43), which is highly expressed in astrocytes. Gonadectomized rats received hormone treatments that induce maximal sexual behavior and gonadotropin surges in females (estrogen for 48 h followed by progesterone, estrogen alone or progesterone alone). Control animals received vehicle (oil) injections. In the female rat preoptic area (POA), containing the gonadotropin-releasing hormone (GnRH) cell bodies, treatment with estrogen, progesterone or estrogen + progesterone significantly increased CX43 protein levels in immunoblots. In contrast, estrogen + progesterone significantly decreased CX43 levels in the male rat POA. This sexually dimorphic hormonal regulation of CX43 was not evident in the hypothalamus, which contains primarily GnRH nerve terminals. Treatment with estrogen + progesterone significantly decreased CX43 levels in both the male and female hypothalamus. To examine the role of CX43 in female reproductive function, we studied heterozygous female CX43 (CX43+/-) mice. Most mutant mice did not show normal estrous cycles. In addition, when compared to wild type females, CX43+/- mice had reduced lordosis behavior. These data suggest that hypothalamic CX43 expression is regulated by steroid hormones in a brain-region-specific and sexually dimorphic manner. Therefore, gap junctional communication in the POA and hypothalamus may be a factor regulating the estrous cycle and sexual behavior in female rodents.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15910768&dopt=Abstract progesterone, progesterone cream