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Response of plasma cortisol and progesterone after ACTH challenge in ovariectomized lactating dairy cows.

Yoshida C, Nakao T.

Department of Animal Science, Graduate School for International Development and Cooperation (IDEC), Hiroshima University, Hiroshima, Japan.

Shortened and weakened estrous expressions could be one of the causes of poor heat detection rate. Non-specific acute stresses are assumed to depress expression of estrus by an increase of plasma progesterone which may originate from the adrenal cortex. The objective of the present study was to examine whether the adrenal cortex can secrete significant amounts of progesterone in response to exogenous adrenocorticotropic hormone (ACTH) in lactating cows. Four cows had estrus synchronized and were ovariectomized in the luteal phase. The cows were given 25 IU ACTH through an indwelling catheter 5 h after catheterization. Blood samples were collected at an interval of 30 min. In 3 of the 4 cows, plasma progesterone concentrations increased significantly 0.5-1.5 h after the first ACTH challenge with a mean peak value of 4.2 +/- 0.4 (S.D.) ng/ml. A similar response was also observed after the second ACTH challenge. Peak plasma progesterone concentrations in the 3 cows after first ACTH challenge were comparable with the progesterone values in the luteal phase of each cow. The results suggest that lactating cows have the capability to secrete a significant amount of progesterone from the adrenal cortex.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15750301&dopt=Abstract progesterone, progesterone cream



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Plasma progesterone concentration depends on sampling site in pigs.

Virolainen JV, Love RJ, Tast A, Peltoniemi OA.

Department of Clinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, Pohjoinen Pikatie 800, 04920 Saarentaus, Finland. juha.v.virolainen helsinki.fi

The objective of this study was to examine a possible difference in progesterone concentrations between the systemic venous blood and the caudal vena cava in early pregnant gilts. Nineteen crossbred pregnant gilts were offered three different regimens of feeding to examine influence of feeding on the secretion pattern of progesterone. The groups were high (H-H), low (L-L) and low-high (L-H) receiving 3.6, 1.8 and 1.8/3.6 kg/day, respectively. Catheters were placed in a jugular vein and the caudal vena cava (to sample ovarian secretion) on day 19 of pregnancy. Two consecutive samples taken at 30-min intervals were collected four times a day for 5 days (days 20-24). In addition, three gilts were simultaneously sampled from both catheters at 30-min intervals for 12 h on day 22. Progesterone concentration was significantly lower in the jugular vein compared with the caudal vena cava in all three feeding groups (P<0.001). An indication of episodic pattern of progesterone production occurred in plasma collected from the caudal vena cava, but not from the jugular vein. Dietary intake did not cause a profound effect on plasma progesterone concentrations during days 20-24 of gestation. It seemed that ovarian progesterone was released into the vena cava in an episodic pattern and there were implications that these episodes were temporally associated with LH pulses.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15766808&dopt=Abstract progesterone, progesterone cream



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[Prevention of recurrent preterm birth: a comeback for progesterone?]

[Article in French]

Carbonne B, Rosenblatt J.

Service de Gynecologie Obstetrique, Hopital Saint-Antoine, 184, rue du Faubourg-Saint-Antoine, 75012 Paris.

Progesterone has been prescribed for many years in women with preterm labor despite the lack of benefit for the fetus or neonate. The description of increased risk of intrahepatic cholestasis of pregnancy led to discontinuation of this prescription. Recently, several double-blind randomized trials have focused on the usefulness of progesterone for the prevention of recurrent preterm birth. In this review, we re-examine the pathophysiological rationale for the use of progesterone and discuss the biases and limitations of older studies, detailing two recent randomized trials which suggest use of progesterone should be revisited. Data from these trials appear to provide convincing evidence that preventive use of 17 alpha-hydroxyprogesterone administered by injections early in the course of pregnancy is effective only for women with a history of preterm delivery. This prescription could be part of a more global preventive strategy together with cervical cerclage and preventive treatment of bacterial vaginitis. During treatment, it is advisable to search for secondary hepatic effects. Conversely, there are still no data favoring the use of progesterone for preterm labor. Most preterm deliveries occurring in women without a history of preterm birth preventive use of progesterone should remain a rare indication.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15767943&dopt=Abstract progesterone, progesterone cream



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Percutaneous administration of progesterone: blood levels and endometrial protection.

Stanczyk FZ, Paulson RJ, Roy S.

Department of Obstetrics and Gynecology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA. fstanczyk socal.rr.com

There is controversy about the beneficial effects of topical progesterone creams used by postmenopausal women. A major concern is that serum progesterone levels achieved with progesterone creams are too low to have a secretory effect on the endometrium. However, antiproliferative effects on the endometrium have been demonstrated with progesterone creams when circulating levels of progesterone are low. Thus, effects of topical progesterone creams on the endometrium should not be based on serum progesterone levels, but on histologic examination of the endometrium. Despite the low serum progesterone levels achieved with the creams, salivary progesterone levels are very high, indicating that progesterone levels in serum do not necessarily reflect those in tissues. The mechanism by which the serum progesterone levels remain low is not known. However, one explanation is that after absorption through the skin, the lipophilic ingredients of creams, including progesterone, may have a preference for saturating the fatty layer below the dermis. Because there appears to be rapid uptake and release of steroids by red blood cells passing through capillaries, these cells may play an important role in transporting progesterone to salivary glands and other tissues. In contrast to progesterone creams, progesterone gels are water-soluble and appear to enter the microcirculation rapidly, thus giving rise to elevated serum progesterone levels with progesterone doses comparable to those used in creams.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15772572&dopt=Abstract progesterone, progesterone cream



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The effects of the neurosteroids: pregnenolone, progesterone and dehydroepiandrosterone on muscarinic receptor-induced responses in Xenopus oocytes expressing M(1) and M(3) 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=15778865&dopt=Abstract progesterone, progesterone cream



progesterone cream
The effects of a progesterone metabolite, 5 beta-dihydroprogesterone, on oxytocin receptor binding in human myometrial membranes.

Astle S, Khan RN, Thornton S.

Department of Biological Sciences, University of Warwick, Coventry, UK.

OBJECTIVE: To determine the effect of the progesterone metabolite 5 beta-dihydroprogesterone on human oxytocin receptor binding in myometrial membranes and on whole-cell calcium current in single myometrial cells. DESIGN: Receptor binding studies in human myometrial membranes prepared from biopsies taken before or after the onset of labour and in Chinese hamster ovary cells expressing the human oxytocin receptor. Whole cell patch-clamp experiments were undertaken on isolated myometrial cells. SETTING: University research laboratories and University hospital.Patients undergoing caesarean section at term either prior to or following onset of labour. METHODS: Myometrial biopsies were taken from women undergoing caesarean section. The binding affinities of oxytocin, 5 beta-dihydroprogesterone and atosiban were determined in myometrial membranes and Chinese hamster ovary cells expressing the human oxytocin receptor. The effect of 5 beta-dihydroprogesterone on inward current was also determined in isolated myometrial cells.Receptor binding affinity and electrophysiological inward current. RESULTS: 5 beta-Dihydroprogesterone did not reduce oxytocin receptor binding in myometrial membranes or Chinese hamster ovary cells expressing the human oxytocin receptor. Nor did it influence calcium current under whole-cell patch conditions in single myometrial cells. In contrast, atosiban inhibited binding in myometrial membranes prepared from samples taken either prior to or following labour (K(i) = 112 and 108 nM, respectively). The affinity of atosiban for the oxytocin receptor was much lower than oxytocin (K(i) = 5 and 6 nM in samples taken before or after labour, respectively) in myometrial membranes and in Chinese hamster ovary cells expressing the human oxytocin receptor (K(i) = 63 M and 1 nM for atosiban and oxytocin, respectively). CONCLUSIONS: We conclude that 5 beta-dihydroprogesterone is unlikely to regulate myometrial activity as a result of a direct effect on oxytocin receptor binding or inward calcium current.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12798477&dopt=Abstract progesterone, progesterone cream



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Progesterone can block the preovulatory gonadotropin-releasing hormone/luteinising hormone surge in the ewe by a direct inhibitory action on oestradiol-responsive cells within the hypothalamus.

Richter TA, Robinson JE, Lozano JM, Evans NP.

Laboratory of Neuroendocrinology, The Babraham Institute, Cambridge, UK.

Elevated oestradiol concentrations during the follicular phase stimulate a surge in gonadotropin-releasing hormone (GnRH) and luteinising hormone (LH) concentrations, which leads to ovulation. Progesterone can block the oestradiol-induced GnRH/LH surge, but the mechanism that is involved is unclear. We examined the effect of progesterone on oestradiol-induced activation of cells within the ovine hypothalamus/preoptic area (POA) to determine: (i) in which regions progesterone acts to block the GnRH/LH surge and (ii) whether progesterone directly or indirectly prevents activation of oestradiol-responsive cells. Cellular activation was assessed by measuring the number of cells that expressed Fos (an immediate early gene). Exposure to increased oestradiol concentrations in the absence of progesterone (which normally stimulates a LH surge) did not cause any region-specific changes in hypothalamic Fos expression during the activation stage of the LH surge-induction process (Experiment 1). The same treatment significantly increased cellular activation within the POA, lateral septum (LS), and arcuate nucleus at the time of surge onset (Experiment 2). Concurrent exposure to increased oestradiol and progesterone concentrations during the activation stage of the surge-induction process (which normally blocks the LH surge) was associated with significantly reduced cellular activation within the ventromedial hypothalamus and anterior hypothalamic area, relative to the positive controls (oestradiol increment alone) and arcuate nucleus relative to the negative controls (no increment in oestradiol) during the activation stage (Experiment 1). At the time of surge onset (Experiment 2), exposure to progesterone during the activation period prevented the oestradiol-induced increase in cellular activation that occurred in the POA, LS and arcuate nucleus of the positive controls. These results demonstrated that oestradiol and progesterone induced differential region- and time-specific effects on cellular activation within the regions of the ovine brain that generate the preovulatory GnRH/LH surge. Moreover, the lack of cellular activation within the POA, LS and arcuate nucleus at the time of surge onset in animals exposed to progesterone during the activation stage is consistent with the hypothesis that progesterone can block the preovulatory surge by direct inhibition of oestradiol-induced cellular activation in these areas.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15796768&dopt=Abstract progesterone, progesterone cream









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