progesterone cream
Stimulation of progesterone production in human granulosa-lutein cells by lipoproteins: evidence for cholesterol-independent actions of high-density lipoproteins.

Ragoobir J, Abayasekara DR, Bruckdorfer KR, Michael AE.

Department of Biochemistry and Molecular Biology, Royal Free and University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK. jragoobir rvc.ac.uk

Low-density lipoproteins (LDL) have been consistently reported to stimulate ovarian steroidogenesis, apparently by the provision of cholesterol as a steroidogenic substrate. Recent studies suggest that high-density lipoproteins (HDL) can also deliver cholesterol to support progesterone synthesis in human granulosa-lutein cells. Therefore, this study investigated the contributions of (i) cholesterol delivery, (ii) cyclic AMP and (iii) protein kinase C (PKC) in the steroidogenic responses of human granulosa-lutein cells to HDL and LDL. Over a 24-h treatment incubation, HDL stimulated a larger increase in progesterone output than did LDL at equivalent cholesterol concentrations. Moreover, at equal protein concentrations (100 microg protein/ml), HDL doubled progesterone production by cells co-treated with a maximally effective concentration of 22R-hydroxycholesterol, whereas LDL had no effect on the progesterone response to this membrane-permeable sterol. These observations indicate that the progesterone response to HDL is not solely due to the delivery of cholesterol as a steroidogenic substrate. Over 24 h, the stimulation of progesterone synthesis by HDL was additive with the response to a maximally effective concentration of dibutyryl-cAMP, but was unaffected by the down-regulation of PKC activity (by chronic pre-treatment with a tumour-promoting phorbol ester). We have concluded that HDL appears to stimulate progesterone production in human granulosa-lutein cells by a mechanism not solely reliant on cholesterol delivery.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11927389&dopt=Abstract progesterone, progesterone cream



progesterone cream
Effect of the preovulatory LH surge on bovine follicular progesterone receptor mRNA expression.

Cassar CA, Dow MP, Pursley JR, Smith GW.

Department of Animal Science, Michigan State University, 1230D Anthony Hall, East Lansing, MI 48824-1225, USA.

A growing body of evidence indicates that intrafollicular progesterone receptor signaling pathways are obligatory for follicle rupture. However, the intrafollicular localization and regulation of progesterone receptor expression during the periovulatory period in cattle are not known. In this study, we determined the effect of the preovulatory gonadotropin surge on localization and expression of progesterone receptor mRNA in bovine periovulatory follicular and luteal tissue. Ovaries containing preovulatory follicles or new corpora lutea (CL) were collected at approximately 0, 6, 12, 18, 24 (preovulatory follicles) and 48 h (CL) after a GnRH-induced LH surge (n=5-8 per timepoint). Expression of progesterone receptor mRNA was detected in periovulatory follicular and luteal tissue at all timepoints examined. Relative levels of progesterone receptor mRNA were dramatically upregulated within 6h after the LH surge compared to all other time points (P<0.0001). In situ hybridization analysis revealed that the significant increase in progesterone receptor mRNA expression was localized to the granulosal layer of preovulatory follicles. Our results indicate that progesterone receptor mRNA expression is upregulated specifically in the granulosal layer of bovine preovulatory follicles following the LH surge. Progesterone receptor signaling pathways may help mediate the effects of the preovulatory LH surge on follicle rupture in cattle.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11934526&dopt=Abstract progesterone, progesterone cream



progesterone cream
Progesterone increases susceptibility of gilts to uterine infections after intrauterine inoculation with infectious bacteria.

Wulster-Radcliffe MC, Seals RC, Lewis GS.

Bioanalytical Systems, Inc., West Lafayette, IN 47906-1382, USA.

In cattle and sheep, a progestogenated uterus is susceptible to infections, but this is not well documented for pigs. Therefore, the effects of day of the estrous cycle and progesterone on the susceptibility to uterine infections were evaluated. Gilts (n = 5 per group) were assigned to treatments in 2 x 2 factorial arrays. In Exp. 1, day of cycle and bacterial challenge were main effects. On d 0 or 8, uteri were inoculated with either 70 x 10(7) cfu of Escherichia coli and 150 x 10(7) cfu of Arcanobacterium pyogenes in PBS or with PBS. In Exp. 2, ovariectomy (OVEX) and progesterone treatment were main effects. On d 0, gilts were ovariectomized or a sham procedure was performed. After surgery, gilts received i.m. injections of progesterone (10 mg/5 mL) or 5 mL of safflower oil diluent twice daily. On d 8, gilts were inoculated with the same doses of bacteria as in Exp. 1. In Exp. 1 and 2, vena caval blood was collected for 4 d, after which uteri were collected. Sediment and ability to culture E. coli and A. pyogenes from uterine flushings were used to diagnose infections. Differential white blood cell counts and lymphocyte response to concanavalin A (Con A) and lipopolysaccharides (LPS) were used to measure lymphocyte proliferation. Progesterone, estradiol-17beta, prostaglandin F2alpha, (PGF2alpha), and prostaglandin E2 (PGE2) were measured in vena caval blood. In Exp. 1, d-8 gilts receiving bacteria developed infections, but d-0 gilts receiving bacteria did not. Daily percentages of neutrophils and lymphocytes changed (P < 0.05) with cycle day and bacterial challenge. Basal- and Con A-stimulated lymphocyte proliferation were greater (P < 0.05) for d-0 than for d-8 gilts. Concentrations of PGF2, (P < 0.01) and PGE2 (P < 0.05) increased after bacterial challenge, regardless of stage of the estrous cycle at the time of inoculation. In Exp. 2, OVEX decreased (P < 0.001) and progesterone treatment increased (P < 0.001) progesterone concentrations, and OVEX decreased (P < 0.01) estradiol-17beta. Gilts with ovarian and/or exogenous progesterone developed infections. Daily percentages of neutrophils and lymphocytes changed in response to OVEX, and neutrophils changed (P < 0.05) in response to endogenous and exogenous progesterone. Lymphocyte proliferation in response to Con A and LPS increased (P < 0.05) with OVEX and decreased (P < 0.05) with progesterone treatment. We conclude that endogenous and exogenous progesterone reduce the ability of the uterus in gilts to resist infections.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12772852&dopt=Abstract progesterone, progesterone cream



progesterone cream
Dendritic spine formation in response to progesterone synthesized de novo in the developing Purkinje cell in rats.

Sakamoto H, Ukena K, Tsutsui K.

Laboratory of Brain Science, Faculty of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima, Japan.

The cerebellar Purkinje cell (PC) is a typical site for neurosteroid formation. We have demonstrated that this neuron possesses intranuclear receptor for progesterone and actively synthesizes progesterone de novo from cholesterol only during rat neonatal life, when the formation of the cerebellar cortex occurs dramatically. In this study, we therefore analyzed the effect of progesterone on dendritic spine formation of the PC. In vitro studies using cerebellar slice cultures from newborn rats showed that progesterone increases the density of PC dendritic spines in a dose-dependent manner. This effect was blocked by the progesterone receptor antagonist, RU486. Furthermore, trilostane, a specific inhibitor of progesterone synthesis, inhibited the increase of spine density. These results suggest that progesterone can promote dendritic spine formation, and endogenous progesterone synthesized de novo in the developing PC may induce such an effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11958856&dopt=Abstract progesterone, progesterone cream



progesterone cream
Demonstration of mixed properties of RU486 in progesterone receptor (PR)-transfected MDA-MB-231 cells: a model for studying the functions of progesterone analogues.

Lin VC, Aw SE, Ng EH, Ng EH, Tan MG.

Department of Clinical Research, Singapore General Hospital, Republic of Singapore 169608.

Progesterone antagonist RU486 (mifepristone) has been implicated for many anti-neoplastic and obstetrical applications. But the compound has demonstrated undesired agonist-like effect depending on cell, tissue and species studied. Using PR-transfected breast cancer cells MDA-MB-231, this report describes the similarities and differences between progesterone- and RU486-mediated effects on cell growth, cell differentiation and, at the molecular level, on the activation of p44/p42 MAP kinases (MAPK). Like progesterone, RU486 inhibited cells growth by arresting the cells in G0/G1 phase of the cell cycle. In contrast to progesterone that induced cell spreading, RU486 induced a multipolar, stellate morphology. RU486-treated cells showed no increase of stress fibers, nor was there any increase of focal adhesions as progesterone-treated cells did. Furthermore, despite of the fact that both compounds inhibited cell growth, RU486 significantly stimulated the activation of p44/p42 MAP kinases whereas progesterone markedly inhibited the activation. Nonetheless, the effects of RU486 were PR-mediated and RU486 was able to antagonize the effect of progesterone on cell growth and focal adhesion. In conclusion, RU486 can act not only as a progesterone antagonist, a progesterone agonist but also induced morphological and molecular changes that were distinct from progesterone-mediated effects in PR-transfected MDA-MB-231 cells. The non-progesterone-like effect of RU486 may be mediated through a pathway that is different from the progesterone-mediated pathway, or it is the result of a blockade of certain critical step(s) in the progesterone-mediated pathway. In any case, undesired side effects of antiprogestin may create clinical complications. PR-transfected MDA-MB-231 breast cancer cells provide a model for studying the functions of progesterone analogues.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11747343&dopt=Abstract progesterone, progesterone cream



progesterone cream
Role of oestradiol in growth of follicles and follicle deviation in heifers.

Beg MA, Meira C, Bergfelt DR, Ginther OJ.

Department of Animal Health and Biomedical Sciences, University of Wisconsin, Madison, WI 53706, USA; and The Eutheria Foundation, Cross Plains, WI 53528, USA.

Follicle deviation is characterized by continued growth of the largest (developing dominant) follicle and reduced growth of the smaller (subordinate) follicles. The aim of the present study was to test the following hypotheses: (1). oestradiol contributes to the depression of circulating FSH encompassing follicle deviation and (2). oestradiol plays a role in the initiation of deviation. Heifers were treated with progesterone (n = 5) or antiserum against oestradiol (n = 7) or given no treatment (control; n = 6). On the basis of previous studies, progesterone treatment would decrease LH and thereby the circulatory and intrafollicular concentrations of oestradiol and the antiserum would reduce the availability of oestradiol. Progesterone was given in six 75 mg injections at 12 h intervals beginning when the largest follicle of wave 1 first reached >or=5.7 mm (t = 0 h). Oestradiol antiserum (100 ml) was given in a single injection at t = 12 h. Follicles of the wave were defined as F1 (largest) and F2, according to the diameter at each examination. Blood samples were collected at 12 h intervals during t = 0-72 h. Treatment with progesterone lowered the circulatory concentrations of LH by 12 h after the start of treatment (P < 0.05), and concentrations remained low compared with those of controls during the treatment period. Treatment with oestradiol antiserum had no effect on LH. Both progesterone and the antiserum treatments increased the FSH concentrations compared with controls (P < 0.05), which supports the first hypothesis. The interval from t = 0 h to the beginning of deviation was longer in the progesterone- (51.0 +/- 7.6 h; P < 0.06) and antiserum (51.4 +/- 6.3 h; P < 0.05)-treated groups than in the controls (38.0 +/- 3.7 h), which supports the second hypothesis. There was no difference among groups in the diameters of F1 and F2 at deviation. Reduced diameter (P < 0.05 or P < 0.06) of both F1 and F2 occurred in both the progesterone- and antiserum-treated groups at t = 36 h and 48 h, compared with controls. Follicle retardation occurred in both the progesterone- and antiserum-treated groups despite the high FSH concentrations, whereas LH was altered only in the progesterone-treated group. Therefore, the follicle effect can be attributed to inadequate intrafollicular oestradiol. This interpretation implies a functional local role for oestradiol in the deviation process, independent of the systemic negative effect on FSH.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12773107&dopt=Abstract progesterone, progesterone cream



progesterone cream
Accuracy of single measurements of pregnancy-associated plasma protein-A, human chorionic gonadotropin and progesterone in the diagnosis of early pregnancy failure.

Dumps P, Meisser A, Pons D, Morales MA, Anguenot JL, Campana A, Bischof P.

Department of Obstetrics and Gynaecology, University of Geneva, Geneva, Switzerland.

BACKGROUND: Circulating human chorionic gonadotropin (hCG) and progesterone are commonly used as markers of abnormal pregnancies. Previous studies have shown that pregnancy-associated plasma protein-A (PAPP-A) was also depressed in extrauterine pregnancies (EUP). Previously, PAPP-A was measured with polyclonal antibodies which were later shown to recognise also the pro-form of major basic protein (pro-MBP). OBJECTIVE: To evaluate the clinical usefulness of PAPP-A measurements in early pregnancy. STUDY DESIGN: Circulating PAPP-A, hCG and progesterone were measured in patients with EUP (n=68), abnormal intrauterine pregnancies (abIUP, n=31) and normal intrauterine pregnancies (nIUP, n=72). Gestational age was 30-70 days from the last menstruation. RESULTS: For PAPP-A and hCG, a steep increase was observed from day 30 after last menstrual period onwards, this increase being much less important for abIUP and EUP. The values of PAPP-A and hCG were significantly decreased in abIUP and EUP, from 42 days after LMP onwards. There were no significant differences between abIUP and EUP. Progesterone concentration does not vary with amenorrhoea and was significantly lower in abIUP and EUP. Values in abIUP were significantly (P=0.02) lower compared with EUP for amenorrhoea above 42 days. ROC curves were constructed for amenorrhoea above 42 days. For a specificity of 99%, the sensitivity of PAPP-A, hCG and progesterone were 64.5, 93.3 and 76%, respectively. The threshold values were 14.3mIU/l, 10,400IU/l and 10.1ng/ml for PAPP-A, hCG and progesterone. CONCLUSION: We confirm the decrease of PAPP-A concentrations in pregnancy failure, but hCG and progesterone remain the best clinical tools.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11750960&dopt=Abstract progesterone, progesterone cream