progesterone cream
Progesterone attenuates the effect of the 5-HT1A receptor agonist, 8-OH-DPAT, and of mild restraint on lordosis behavior.

Truitt W, Harrison L, Guptarak J, White S, Hiegel C, Uphouse L.

Department of Biology, Texas Woman's University, PO Box 425799, Denton 76204-5799, USA.

Ovariectomized, hormone-primed rats were used to test the hypothesis that progesterone treatment attenuated the effects of the 5-HT(1A) receptor agonist, (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), on female rat lordosis behavior. Based upon prior evidence that prepriming with estradiol benzoate (EB) reduced the ability of 8-OH-DPAT to inhibit lordosis behavior, rats were preprimed with 10 microg EB 7 days before a second priming with 10 microg EB followed 48 h later with 500 microg progesterone or vehicle. Independent of the presence of progesterone, prepriming with EB attenuated the lordosis-inhibiting effects of systemic treatment with 8-OH-DPAT. However, progesterone also reduced the effects of 8-OH-DPAT and this effect was also seen in females primed only once with EB. In contrast, progesterone was relatively ineffective in attenuating the effects of bilateral infusion with 8-OH-DPAT into the ventromedial nucleus of the hypothalamus (VMN). The failure of progesterone to substantially reduce the effects of VMN infusion with 8-OH-DPAT contrasts with prior studies in which estrogen's protective action against the drug did include the VMN. Thus, while both estrogen and progesterone reduce the lordosis-inhibiting effect of 8-OH-DPAT, the mechanisms responsible for the effects of the two gonadal hormones may be different. Priming with progesterone also prevented the effects of 5 min of restraint. When rats were hormonally primed with EB and oil, rats showed a transient, but significant, decline in lordosis behavior 5 and 10 min after restraint. Rats primed with EB and progesterone were unaffected by the restraint. These results are discussed in terms of their implications for the role of progesterone in altering the 5-HT(1A) receptor modulation of lordosis behavior.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12742638&dopt=Abstract progesterone, progesterone cream



progesterone cream
Action of progesterone on contractile activity of isolated gastric strips in rats.

Wang F, Zheng TZ, Li W, Qu SY, He DY.

Insititute of Infectious Diseases, the Third Military Medical University Afflicated Southwest Hospital, Chongqing 400038, China. kaixin919 163.com

AIM: To study the effect of progesterone on contractile activity of isolated gastric strips in rats. METHODS: Wistar rats were sacrificed to remove whole stomach. Then, the stomach was opened and the mucosal layer was removed. Parallel to either the circular or the longitudinal fibers, muscle strips were cut from fundus, body, antrum and pylorus. Each muscle strip was suspended in a tissue chamber containing 5 mL Krebs solution. Then the motility of gastric strips in tissue chambers was simultaneously recorded. The preparations were subjected to 1 g load tension and washed with 5 ml Krebs solution every 20 min. After 1 h equilibration, progesterone or antagonists were added in the tissue chamber separately. The antagonists were added 3 min before using progesterone (50 micromol/L(-1)). RESULTS: Progesterone decreased the resting tension of fundus and body longitudinal muscle (LM) (P<0.05). It inhibited the mean contractile amplitude of body and antrum LM and circular muscle (CM), and the motility index of pyloric CM (P<0.05). The inhibition of progesterone on the mean contractile amplitude could be partially blocked by phentolamine in LM of the stomach body (the mean contractile amplitude of body LM decreased from -7.5+/-5.5 to -5.2+/-4.5 P<0.01), and by phentolamine or indomethacin in CM of body (The inhibition of progesterone on the mean contractile amplitude of body CM decreased from -5.6+/-3.0 to -3.6+/-2.7 by phentolamine and from -5.6+/-3.0 to -3.5+/-2.5 by indomethacin, P<0.01). Hexamethonium, propranolol and L-NNA (inhibitor of NO synthetase) didn't affect the action of progesterone (P>0.05). CONCLUSION: The study suggested that progesterone can inhibit the contractile activity of isolated gastric strips in rats and the mechanism seems to be a direct one except that the action on gastric body is mediated through prostaglandin and adrenergic alpha receptor partly.

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progesterone cream
The kinetics of serum hCG and progesterone in response to oral and vaginal administration of misoprostol during medical termination of early pregnancy.

Honkanen H, Ranta S, Ylikorkala O, Heikinheimo O.

Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki and Department of Biomedicine, University of Helsinki, Helsinki, Finland.

BACKGROUND: Misoprostol is widely used in combination with mifepristone for medical termination of pregnancy. We studied the endocrine parameters of trophoblast function during medical termination of early pregnancy using mifepristone in combination with oral or vaginal misoprostol. The effect of prolonged misoprostol administration was also examined. METHODS: Thirty-four women, requesting termination of pregnancy and with <or=63 days of amenorrhoea, received 200 mg of mifepristone on day 0, followed by either oral (n = 13) or vaginal (n = 21) administration of 0.8 mg of misoprostol on day 2. In 23 cases misoprostol administration was continued orally for an additional 7 days. Serum samples, collected up to 14 days following the beginning of the treatment, were analysed for hCG, progesterone and mifepristone. RESULTS: hCG and progesterone concentrations continued to increase until day 2. Following misoprostol, hCG and progesterone levels declined by 70.5 +/- 8.8% and 61.3 +/- 16.3% (mean +/- SD) respectively, in 24 h. The percentage decline in hCG correlated inversely (P < 0.05) with the time taken to abort. The peak level of mifepristone measured on day 2 did not correlate with the decline in serum hCG or progesterone. The kinetics of hCG, progesterone and mifepristone were similar in the different treatment groups. CONCLUSIONS: The route and duration of misoprostol administration have no effect on the kinetics of serum hCG or progesterone during medical termination of early pregnancy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12202418&dopt=Abstract progesterone, progesterone cream



progesterone cream
Interaction between carbohydrate residues of alpha(1)-acid glycoprotein (orosomucoid) and progesterone. A fluorescence study.

De Ceukeleire M, Albani JR.

Laboratoire de Biophysique Moleculaire, Universite des Sciences et Technologies de Lille, Batiment C6, 59655 Villeneuve d'Ascq Cedex, France.

Interaction between progesterone and the carbohydrate residues of alpha(1)-acid glycoprotein was followed by fluorescence studies using calcofluor white. The fluorophore interacts with polysaccharides and is commonly used in clinical studies. Binding of progesterone to the protein induces a decrease in the fluorescence intensity of calcofluor white, accompanied by a shift to the short wavelengths of its emission maximum. The dissociation constant of the complex was found equal to 8.62 microM. Interaction between progesterone and free calcofluor in solution induces a low decrease in the fluorescence intensity of the fluorophore without any shift of the emission maximum. These results show that in alpha(1)-acid glycoprotein, the binding site of progesterone is very close to the carbohydrate residues. Fluorescence intensity quenching of free calcofluor in solution with cesium ion gives a bimolecular diffusion constant (k(q)) of 2.23 x 10(9) M(-1) s(-1). This value decreases to 0.19 x 10(9) M(-1) s(-1) when calcofluor white is bound to alpha(1)-acid glycoprotein. Binding of progesterone does not modify the value of k(q) of the cesium. Previous studies have shown that the terminal sialic acid residue is mobile, while the other glycannes are rigid [Albani, J. R.; Sillen, A.; Coddeville, B.; Plancke, Y. D.; Engelborghs, Y. Carbohydr. Res. 1999, 322, 87-94]. Red-edge excitation spectra and Perrin plot experiments performed on sialylated and asialylated alpha(1)-acid glycoprotein show that binding of progesterone to alpha(1)-acid glycoprotein does not modify the local dynamics of the carbohydrate residues of the protein.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12204624&dopt=Abstract progesterone, progesterone cream



progesterone cream
Relationship between asymptomatic hypercholanaemia of pregnancy and progesterone metabolism.

Pascual MJ, Serrano MA, El-Mir MY, Macias RI, Jimenez F, Marin JJ.

University Hospital, University of Salamanca, 37007-Salamanca, Spain.

The aim of this study was to identify a subgroup of pregnant women with asymptomatic hypercholanaemia of pregnancy (AHP), in which the relationship between alterations in the level and pattern of serum bile acids (BAs) and of progesterone plus progesterone metabolites could be investigated in the absence of overt impairment of hepatobiliary function. Cholanaemia and serum concentrations of progesterone were assayed by an enzymic technique and by ELISA respectively, while BA molecular species and progesterone metabolites were measured by GC-MS, in the serum of 411 healthy pregnant women. Samples were collected after an overnight fast in the final week of each trimester of gestation. Two pregnant women were excluded because of the suspicion of intrahepatic cholestasis of pregnancy (ICP). Cholanaemia was found to increase progressively throughout pregnancy, but with normal mean values lower than 3.0 microM. Thus in our series AHP was defined arbitrarily as the presence of serum total BA concentrations 2-fold higher than this value, i.e. 6 microM, in the absence of hepatobiliary disease or symptoms of ICP. The prevalence of this condition was observed to increase with gestational age. Changes in the pattern of serum BAs in AHP were also found. These were reflected in a marked increase in the proportion of cholic acid together with a decrease in that of deoxycholic acid, while the proportions of chenodeoxycholic acid and lithocholic acid changed only moderately. When groups at the same gestational age were compared, serum progesterone levels were always significantly lower, while those of progesterone metabolites were higher, in women with AHP. Our results suggest that AHP is a relatively common condition in our geographical location, where ICP is rarely diagnosed. Changes in the serum BA pattern in hypercholanaemia resemble these described in ICP. The simultaneous finding of lower serum total progesterone levels along with an increase in its metabolites supports the hypothesis that a primary defect in progesterone metabolism may be involved in the aetiology of ICP.

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progesterone cream
Distribution and metabolism of topically applied progesterone in a rat model.

Waddell BJ, O'Leary PC.

Department of Anatomy and Human Biology, The University of Western Australia, 35 Stirling Highway, Crawley, Perth, WA 6009, Australia. bwaddell anhb.uwa.edu.au

This study investigated the transdermal uptake and subsequent tissue distribution of [(3)H]progesterone applied in a commercially available progesterone cream in a rat model. Concentrations of lipid- and water-soluble metabolites of [(3)H]progesterone were also measured in plasma, urine and selected tissues (uterus, liver, kidney, salivary gland) 3 h after its topical application. Female rats were ovariectomized and adrenalectomized to remove all endogenous progesterone, and 4 weeks later were anaesthetized and 150 mg Pro-Feme cream (containing progesterone 3.2% w/w and 200 microCi [(3)H]progesterone) was applied to the abdominal skin. Six arterial blood samples were then obtained from a carotid cannula over the following 3h, and urine and selected tissue samples were collected after the final blood sample. Plasma progesterone increased progressively until 90 min, then remained relatively stable. Plasma levels of [(3H)]progesterone were high by the 15-min sample and increased only slightly thereafter. Water-soluble metabolites were detectable in plasma at 15 min, whereas lipid-soluble metabolites became apparent only by 60 min then increased progressively to 180 min. The tissue:plasma concentration ratio for [(3)H]progesterone exceeded 1 in all tissues, most notably in uterus (8.4) and lung (9.6), whereas urinary [(3)H]progesterone levels were only half those in plasma. Concentrations of lipid- and water-soluble progesterone metabolites were most prevalent in liver and kidney, and both reached very high concentrations in urine. These results demonstrate that topically applied progesterone is rapidly absorbed transdermally and that its patterns of distribution and metabolism are comparable to those previously reported for intravascularly administered progesterone.

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progesterone cream
Biotransformation of steroids by a recombinant yeast strain expressing bovine cytochrome P-45017alpha.

Shkumatov VM, Usova EV, Poljakov YS, Frolova NS, Radyuk VG, Mauersberger S, Chernogolov AA, Honeck H, Schunck WH.

Research Institute for Physical Chemical Problems, Belarussian State University, Minsk, 220050, Belarus. biopharm bsu.by

The cDNA encoding cytochrome P-45017alpha from bovine adrenal cortex was expressed in Saccharomyces cerevisiae under the control of the galactose-inducible GAL10 promoter. Carbon monoxide difference spectra of the galactose-induced yeast cells showed expression of about 240 nmol of P-45017alpha per liter of the culture. Binding of progesterone to the cytochrome P-45017alpha was clearly detectable already with intact yeast cells as judged by the formation of type I substrate difference spectra. Yeast cells grown on minimal medium containing galactose actively converted progesterone to 17alpha-hydroxyprogesterone, this indicating the functional integrity of the heterologously expressed P-45017alpha and its efficient coupling with the constitutive NADPH-cytochrome P-450 reductase. More than 80% of the metabolite produced was secreted into the culture medium. Cultivation in a rich non-selective medium resulted in the formation of an additional product, which was identified by mass spectrometry as 17alpha-hydroxy-20-dihydroprogesterone. Kinetic analysis revealed that its production followed the cytochrome P-45017alpha-dependent hydroxylation reaction. The reduction of the 20-keto group of 17alpha-hydroxyprogesterone was also observed in the non-induced yeast culture, this suggesting the involvement of the constitutive enzyme. Among several substrates tested, progesterone was hydroxylated by the cytochrome P-45017alpha expressed with the highest activity. The activity towards other substrates decreased in the sequence: 11beta- > 11alpha- > 19-hydroxyprogesterone. In conclusion, the present results show that the host-vector system used is suitable for high-level functional expression of P-45017alpha and further application of enzymatic properties of this protein to perform specific steroid biotransformations.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11996660&dopt=Abstract progesterone, progesterone cream