Effect Of Endogenous Progesterone Research Articles

Effect of progesterone on Smad signaling and TGF-β/Smad-regulated genes in lung epithelial cells.

The effect of endogenous progesterone and/or exogenous pre- or postnatal progesterone application on lung function of preterm infants is poorly defined. While prenatal progesterone substitution may prevent preterm birth, in vitro and in vivo data suggest a benefit of postnatal progesterone replacement on the incidence and severity of bronchopulmonary dysplasia (BPD). However, the molecular mechanisms responsible for progesterone’s effects are undefined. Numerous factors are involved in lung development, airway inflammation, and airway remodeling: the transforming growth factor beta (TGF-β)/mothers against decapentaplegic homolog (Smad) signaling pathway and TGF-β-regulated genes, such as connective tissue growth factor (CTGF), transgelin (TAGLN), and plasminogen activator inhibitor-1 (PAI-1). These processes contribute to the development of BPD. The aim of the present study was to clarify whether progesterone could affect TGF-β1-activated Smad signaling and CTGF/transgelin/PAI-1 expression in lung epithelial cells. The pharmacological effect of progesterone on Smad signaling was investigated using a TGF-β1-inducible luciferase reporter and western blotting analysis of phosphorylated Smad2/3 in A549 lung epithelial cells. The regulation of CTGF, transgelin, and PAI-1 expression by progesterone was studied using a promoter-based luciferase reporter, quantitative real-time PCR, and western blotting in the same cell line. While progesterone alone had no direct effect on Smad signaling in lung epithelial cells, it dose-dependently inhibited TGF-β1-induced Smad3 phosphorylation, as shown by luciferase assays and western blotting analysis. Progesterone also antagonized the TGF-β1/Smad-induced upregulation of CTGF, transgelin, and PAI-1 at the promoter, mRNA, and/or protein levels. The present study highlights possible new molecular mechanisms involving progesterone, including inhibition of TGF-β1-activated Smad signaling and TGF-β1-regulated genes involved in BPD pathogenesis, which are likely to attenuate the development of BPD by inhibiting TGF-β1-mediated airway remodeling. Understanding these mechanisms might help to explain the effects of pre- or postnatal application of progesterone on lung diseases of preterm infants.

Is medroxyprogesterone safe in women with long QT syndrome?

G Twenty-two percent of women in the United States use depot medroxyprogesterone acetate (MPA) at some stage in their life for contraception. It is highly effective, can be elf-administered, and has high adherence rates. The World ealth Organization lists it as a first-line option for young omen, particularly those wishing to avoid the adverse ffects of estrogens, such as breast-feeding mothers, smokrs, those who are overweight, and those with atrial fibrilation, pulmonary hypertension, valvular heart disease, and ypertension in pregnancy. Thus, when a case report apears suggesting a possible link between MPA and QT rolongation with cardiac arrest, the evidence needs to be eviewed carefully; the impact of withdrawal or even cauion with MPA could be massive. Giudicessi et al report a woman with a frame shift mutation in KCNH2 (long QT type 2) who in her midtwenties had 2 episodes of ventricular arrhythmia with a prolonged QT interval while taking MPA over a period of 16 months overall. Once MPA was discontinued, no further events occurred over the next 6 years, including 2 further uneventful pregnancies and postpartum periods. Women are more prone than men to the QT-prolonging effects of drugs. Most such drugs exert their effect on the otassium channel IKr, the channel that is defective in long T syndrome type 2. Nevertheless, the case comes as a urprise since it seems beyond doubt both from clinical and n vitro studies that while estrogen prolongs the QT interval, rogesterone (and testosterone) shortens it. The QT-proonging effects of some drugs, for example, ibutilide, are itigated by progesterone. During pregnancy in long QT type 2, the risk of cardiac events is reduced. This is believed to be due to the protective (QT-shortening) effect of endogenous progesterone. During the postpartum period, the protective effect of endogenous progesterone disappears and there is an immediate high risk of cardiac events. In a transgenic rabbit model of long QT type 2, progesterone reduces the incidence of arrhythmia.

Effect of endogenous progesterone and oestradiol-17β on the incidence of gastro-oesophageal reflux and on the barrier pressure during general anaesthesia in the female dog

ObjectiveTo investigate the potential effect of increased blood progesterone (P4) and oestradiol-17β (E2) concentrations on the barrier pressure (BrP) and the incidence of gastro-oesophageal reflux (GOR) in female dogs under general anaesthesia. Study designProspective, blinded experimental trial. AnimalsSeven female, adult, healthy dogs weighing 14–21 kg and aged 1–7 years. MethodsEach of the animals was studied under the influence of high blood E2 and basal P4 (study O), basal E2 and high P4 (study P) and basal E2 and P4 (study C) concentrations. Animals were premedicated with acepromazine and anaesthesia was induced with thiopental and maintained with halothane. Lower oesophageal pH was monitored continuously for 1 hour after induction. GOR was defined as oesophageal pH >7.5 or <4. Manometry of the posterior oesophageal sphincter (POS) was then performed using the slow pull-through technique. ResultsAcid GOR was detected in only one animal of study O. The three studies did not differ significantly in GOR. Mean BrP was 11.2 (study O), 9.1 (study P) and 11.6 mmHg (study C). No significant differences were detected with respect to mean BrP, intra-gastric pressure and POS pressure. ConclusionsIt is unlikely that the increased concentrations of E2 or P4 during the normal ovarian cycle influence the functional efficiency of the POS as a major barrier to GOR in healthy, female dogs under general anaesthesia. Clinical relevanceThe fact that female dogs undergoing obstetrical surgery represented a substantial sub-group of the animals which developed postoperative benign oesophageal stricture, should probably not be attributed to the effects of increased concentrations of female sex steroid hormones.

The effect of endogenous progesterone on basal body temperature in stimulated ovarian cycles.

Whilst it is well recognized that progesterone is involved in the elevation of body temperature following ovulation, the mechanism for this process has not been determined. In this study 87 patients undergoing in-vitro fertilization recorded their basal body temperature during one treatment cycle. Exogenous gonadotrophin therapy administered to induce multiple folliculogenesis considerably elevated periovulatory oestrogen levels and early luteal phase progesterone. Body temperature rapidly rose to plateau 48 h after follicular aspiration in all patients. The amplitude of the temperature rise was independent of the progesterone concentration and the type of hormonal stimulation. There was no correlation between the degree of elevation of progesterone and the amplitude of the rise in body temperature over the first 4 days of the luteal phase. It is postulated that serum progesterone levels do not directly control body temperature, but that an oestrogen-progesterone synergism may be involved.

Regulation of gonadotrophin release by the corpus luteum in the baboon.

Removal of the corpus luteum of the baboon during deturgescence of the perineal sex skin (early stage of the luteal phase) ad-vanced the onset of the next ovarian cycle in 3 out of 4 cases. Progesterone, given as 1 mg every 2 days after removal of the corpus luteum, was unable to reproduce the inhibitory effect of endo-genous progesterone on ovulation in 3 out of 4 baboons, whereas 5 mg progesterone every other day delayed the cycle onset well beyond its usual time. This suggests that withdrawal of circulating progesterone brings about prompt initiation of gonadotrophin secretion and ovarian follicle development. However, removal of the corpus luteum during quiescence of perineal sex skin (middle stage of the luteal phase) did not ad-vance the onset of the next cycle. The implication is either that the corpus luteum in the middle and later stage of the luteal phase is not producing inhibitory levels of progesterone, or that the previous exposure to progesterone has already set in motion a sequence of even...

Effects of an intra-uterine contraceptive device on mitosis in the rat uterus on different days of pregnancy.

Summary. Changes in the pattern of cell division in the rat uterus with an intra-uterine silk thread suture in one horn were studied during the first 5 days of pregnancy. There was no appreciable difference between the mitotic counts in the two horns on Days 1 to 4 of pregnancy, except that there was an increase in the luminal epithelial mitotic count on Day 4 of pregnancy in the horn with the device. There was a marked difference in the luminal mitotic count between the two horns on Days 4 and 5 of pregnancy. While the mean mitotic count was 1·7 in the control horn on Day 5, it was 421 in the horn with the device. The diminution in the mitotic count seen on Day 5 of pregnancy in the control horn was not present in the horn with the device. It is possible that the effect of endogenous progesterone in causing diminished mitosis in the lumen was prevented by the presence of an IUD.