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Premature elevation of progesterone shortens duration of ovulation in PMSG/hCG-treated prepuberal gilts.

A surge of LH during the follicular phase triggers multiple pathways, including progesterone and prostaglandin synthesis before culminating in ovulation. Progesterone has been shown to be involved in the ovulatory process in many species. In prepuberal gilts treated with PMSG/hCG the follicular progesterone level has been shown to increase sharply before ovulation. This study was conducted to investigate whether premature elevation of progesterone can accelerate the ovulatory process in Large White PMSG/hCG-treated prepuberal gilts. Fifty-four Large White gilts were treated with 1000 IU, i.m. PMSG to stimulate follicular growth, followed 72 h later by 500 IU, i.m. hCG to induce ovulation. Gilts in the treatment group (n = 27) were given progesterone intermuscularly at 24 and 36 h after hCG. Ovaries were exteriorized to observe ovulation points during laparotomy under general anesthesia at 38 to 50 h after hCG. Ovulation in both groups commenced by 40.05 h after hCG and was completed by 47.71 h in the control group and by 42.87 h after hCG in the treated group. Progesterone shortened (P < 0.01) ovulation time by 4.84 h and the time required (P < 0.01) for the median proportion of follicles to ovulate (40.7 vs 43.5 h after hCG). Progesterone also increased (P < 0.01) the plasma progesterone concentration without altering follicular progesterone concentration.

Animals↗

Effect of estradiol and progesterone on oviductal LH-receptors and LH-dependent relaxation of the porcine oviduct.

We have previously shown that the porcine oviduct possesses immunoreactive and functional LH receptors and that LH causes relaxation of the oviduct, especially during the periovulatory stage of estrous cycle. The current studies were undertaken to investigate the effects of estradiol and progesterone on LH receptor protein and LH-stimulated motility of the oviduct in steroid-primed ovariectomized gilts. Twenty-one cross-bred gilts were ovariectomized at 6 m.o. of age. Four weeks later gilts received daily intramuscular injection of either 2 mL corn oil (control n = 4), estradiol benzoate (EB) 1.5 mg (n = 6), progesterone 50 mg (n = 5), or 1.5 mg EB plus 50 mg progesterone (n = 6) for 4 consecutive days. The gilts were slaughtered on Day 5 after the first injection of steroids or vehicle. Rings of isthmus and ampulla were collected from each oviduct and placed in a tissue chamber perfused with Kreb's solution for 60 min. The mechanical activity was recorded for 30 min after LH treatment. Immunoreactivity of LHR in the Fallopian tube sections were detected in the epithelium of the tubal mucosa, smooth muscle cells and the blood vessel endothelium. Western blotting showed that porcine oviducts contain 75, 48 and 45 kDa immunoreactive LH receptor proteins, like the corpus luteum (CL). The lowest receptor expression was found in controls and in gilts treated with estradiol or progesterone. Combined treatment with estradiol and progesterone resulted in a significant increase of LH receptor protein concentrations when compared with control animals. In vitro LH treatment affected oviduct contractility of combined estradiol and progesterone treated gilts but not the oviduct of the remaining groups. It also caused a decrease in amplitude, frequency and areas under the curve (AUC) of ampulla (P < 0.05) and the amplitude and AUC of isthmus (P < 0.001) in combined estradiol and progesterone-primed gilts. These results indicate that estradiol and progesterone together, but not separately, increase LH receptor protein in the porcine oviduct and that combined estradiol and progesterone priming is necessary for LH-induced relaxation of the porcine oviduct.

Animals↗

The hormonal control of endometrial receptivity: estrogen (E2) and progesterone.

While the number of identified substances produced by the ovary increases steadily, it remains remarkable that the sole use of exogenous estrogen (E2) and progesterone (P) can prime optimal endometrial receptivity in women whose ovaries have failed or are absent. Early work showed that a marked leeway existed in the acceptable duration of the E2-only phase of endometrial priming. Subsequently, a sequence of transformations are induced by exogenous progesterone that reproduces classical findings made in the menstrual cycle. Secretory changes in endometrial glands are best seen between the 4th and 6th day of progesterone administration (day 18-20 of an ideal cycle where progesterone exposure starts on day 15). Predecidual changes of the endometrial stroma are apparent starting on the 10th day of progesterone exposure (day 24). Contrary to earlier belief, even maximal alterations in the plasma E2 to progesterone ratio fails to alter the endometrial morphology of either glands or stroma. More recently it has been recognized that E2 and progesterone also affect uterine contractility. It has been postulated that excessively high levels of E2 may increase uterine contractility and adversely affect implantation rates in in-vitro fertilization (IVF). Exogenous progesterone has been shown to exert utero-relaxing effects and it has been hypothesised that progesterone supplementation before embryo transfer (ET) may improve receptivity in IVF.

Androgens↗

Progesterone stimulates Krox-20 gene expression in Schwann cells.

The gene of the zinc finger transcription factor Krox-20 (Egr-2) is expressed in Schwann cells and plays an important role in myelination of peripheral nerves. We have shown that progesterone promotes myelination in the regenerating sciatic nerve and in cocultures of Schwann cells and sensory neurones. To determine whether progesterone regulates Krox-20 expression, we measured its effects on Krox-20 mRNA levels in the MSC80 mouse Schwann cell line by semi-quantitative RT-PCR. Although low levels of Krox-20 mRNA are detectable in MSC80 cells cultured in defined medium, treatment with 10(-6) M progesterone induces a rapid (15 min) and transient increase in the levels of Krox-20 mRNA. Lower doses of progesterone (10(-9), 10(-8) and 10(-7) M) are also effective in increasing Krox-20 mRNA. Other steroids including testosterone, dexamethasone, and estradiol are ineffective when added to the culture medium at 10(-6) M for 1 h. The induction of Krox-20 mRNA was also observed with the selective progesterone agonist Organon 2058 and was abolished by treating the MSC80 Schwann cells with the progesterone antagonist RU486, indicating that progesterone induces Krox-20 mRNA expression by binding to its intracellular receptor. The induction of Krox-20 by progesterone was also demonstrated in primary cultures of Schwann cells isolated from neonatal rat sciatic nerves, at the mRNA level by RT-PCR and at the protein level by immunohistochemistry. As Krox-20 is a necessary step for the initiation of myelin formation in peripheral nerves, its stimulation by progesterone suggests an important signalling function for this steroid in myelination.

Animals↗

Plasma progesterone kinetics following surgical treatment of ectopic pregnancies.

OBJECTIVES: Comparative study of plasma progesterone and betaHCG kinetics following surgical treatment of ectopic pregnancy. STUDY DESIGN: Prospective study involving 62 patients with tubal ectopic pregnancies. Study of the kinetics of plasma progesterone and betaHCG, and the correlation coefficient between plasma progesterone and betaHCG levels during post-operative follow-up. RESULTS: Thirty-nine patients were treated by salpingostomy and 23 by salpingectomy. Analyzing the betaHCG kinetics according to treatment revealed that both curves were convergent on day 2. Progesterone kinetics differed greatly in that they appeared "parallel and confused". Analyzing the correlation between betaHCG and progesterone levels proved the absence of a significant link. CONCLUSIONS: Studying the kinetics of plasma progesterone after surgical treatment of ectopic pregnancies revealed a fast decrease in progesterone. Statistical analysis of the progesterone concentration showed that post-operative kinetics is fully independent from that of betaHCG. Progesterone therefore cannot be substituted to betaHCG for post-operative follow-up.

Chorionic Gonadotropin, beta Subunit, Human↗

Regulation of progesterone and prostaglandin F2alpha production in the CL.

After the luteinizing hormone (LH) surge, the cells that remain from the ovulated follicle undergo a process of differentiation termed luteinization. Two key features of the cells after luteinization are the capacity for tremendous production of progesterone [10(16) molecules of progesterone per (min/(g of CL))] and the capacity to undergo regression or death of the cells at the appropriate time. There are two steroidogenic cell types, the small and large luteal cells that are regulated by different mechanisms. In small luteal cells, production of progesterone is stimulated by LH through the protein kinase A (PKA) pathway. The large luteal cells of ruminants produce large quantities of progesterone that is independent of LH stimulation. Although luteotrophins clearly regulate luteal function, much of luteal progesterone production in some species appears to be constitutive, consistent with the autonomous aspects of the large luteal cell. The key regulated step in luteal progesterone production appears to be regulation of transport of cholesterol to the inner mitochondrial membrane apparently mediated by the steroidogenic acute regulatory protein (StAR). In addition, our recent research indicates that PKA is tonically active in large luteal cells and this may be responsible for the high, relatively autonomous nature of luteal progesterone production. Regression of the corpus luteum (CL) in many species is initiated by prostaglandin (PG) F2alpha secreted from the uterus. Luteal cells also have the capacity for production of PGF2alpha. Luteal PGF2alpha production can be regulated by a variety of substances including inhibition by progesterone and stimulation by cytokines. We have also characterized a positive feedback pathway in ruminant and porcine CL in which small amounts of uterine PGF(2alpha) stimulate intraluteal production of PGF2alpha due to induction of the cycloxygenase-2 (Cox-2) enzyme in large luteal cells. This positive feedback pathway is only present in CL that has acquired the capacity for luteal regression ( approximately day 7 in cow, approximately day 13 in pig). Regulation by protein kinase C (PKC) of transcriptional factors interacting with an E-box in the 5' flanking region of the Cox-2 gene is the critical regulatory element involved in this positive feedback pathway. Thus, luteinization in some species appears to change specific gene transcription such that progesterone production becomes relatively independent of acute luteotrophic regulation and intraluteal PGF2alpha synthesis is induced by the second messenger pathways that are activated by PGF2alpha.

Animals↗

Effects of acute progesterone administration in healthy postmenopausal women and normally-cycling women.

The goal of this study was to investigate the behavioral and subjective effects of single doses of progesterone (intramuscular) in post-menopausal women and in women with normal menstrual cycles. Although certain metabolites of progesterone (e.g., allopregnanolone) are known to bind to GABA(A) receptors and produce sedative-like effects in laboratory animals, few studies have examined the acute effects of these neurosteroids in humans. Postmenopausal women (N=10) received progesterone (25, 50, 100 mg im) or placebo at weekly intervals, and women with normal menstrual cycles (N=8) received progesterone (100 mg im) or placebo once a month during the early follicular phase. Dependent measures included plasma levels of progesterone and allopregnanolone, self-report measures of mood and subjective effects and psychomotor performance. Plasma concentrations of progesterone and allopregnanolone increased in a time and dose-dependent manner, with relatively little variability. The concentrations were similar in both groups, although the ratio of allopregnanolone to progesterone was higher in cycling women at certain time points. Contrary to expectations, progesterone produced only modest behavioral or subjective effects. In the cycling women, it produced mild sedative-like effects (i.e., decreases in ratings of Vigor and Friendliness). In the post-menopausal women, only the highest dose (100 mg) slightly increased ratings of feeling "sluggish". These results suggest that progesterone and its metabolites, at concentrations well beyond those attained during the normal menstrual cycle, produce only marginal sedative-like effects. These findings suggest that brief (i.e., several hours) increases in plasma levels of allopregnanolone do not have direct effects on mood.

Affect↗

Utility of serum progesterone and prolactin analysis for assessing reproductive status in the Asian elephant (Elephas maximus).

Concentrations of serum progesterone and prolactin were assessed during the perioestrous period and throughout gestation in the Asian elephant (Elephas maximus) as a means of generating information of potential use to managers. In > 95% of perioestrous periods (n=35), behavioural oestrus (as determined by bull interest, mounting and/or breeding) coincided with the onset of increased serum progesterone concentrations at the beginning of the luteal phase and continued through Day 7 (Day 1 = first significant serum progesterone rise). Within individuals, 1- to 2-day transient decreases (P < 0.05) in serum progesterone occurred between Days 2 and 9. Notably, no sexual behaviour was observed in any female after this transient fall in progesterone. Prolactin concentrations fluctuated randomly throughout the perioestrous period, with no clear pattern. During the study, four females conceived (one conceived twice), and two delivered three viable offspring. Serum progesterone was elevated above baseline throughout gestation, and then declined precipitously 2-3 days before parturition. Serum prolactin concentrations were significantly elevated above baseline (P < 0.05) after 5-6 months of gestation and remained high until after parturition. This study confirms that serum progesterone and prolactin analyses are useful tools for monitoring the reproductive status of Asian elephant females. Specifically, the transition from low to high progesterone secretion during the late interluteal/early luteal phase is predictive of oestrus and can be used to coordinate breeding efforts. Pregnancy can be confirmed by elevated serum prolactin after 6 months postbreeding, whereas the late gestational decrease in progesterone is predictive of impending parturition.

Animals↗

Oxytocin stimulates secretion of prostaglandin F(2alpha) from endometrial cells of swine in the presence of progesterone.

Oxytocin (OT) stimulates endometrial secretion of prostaglandin (PG) F(2 alpha) during corpus luteum regression in swine but there is differential responsiveness to OT among endometrial cell types. To determine if progesterone influenced responsiveness of luminal epithelial, glandular epithelial, and stromal cells to 100 nM OT during luteolysis in swine, cells were isolated from endometrium of 15 gilts by differential enzymatic digestion and sieve filtration on day 16 postestrus and cultured continuously in the presence of 0, 10 or 100 nM progesterone. For phospholipase C (PLC) activity and PGF(2 alpha) secretion, stromal cells were most responsive to OT (P<0.01) in the absence of progesterone, whereas luminal epithelial cells were unresponsive and glandular epithelial cells displayed an intermediate response to OT (P<0.09). Progesterone enhanced PLC activity linearly in glandular epithelial cells (P<0.05) and influenced it quadratically in stromal cells (P=0.05). The effect of OT and progesterone on PLC activity in luminal epithelial cells was not significant, and progesterone did not increase PLC activity in response to OT in any cell type. Culture in the presence of progesterone, enhanced PGF(2 alpha) secretion in response to OT in luminal epithelial cells (P<0.05) but not in glandular epithelial or stromal cells. Progesterone also increased overall PGF(2 alpha) release from glandular epithelial (P<0.05) and stromal cells (P<0.06) across both levels of OT treatment. These results indicate that progesterone enhanced PGF(2 alpha) secretion from luminal epithelial cells in response to OT and increased basal PGF(2 alpha) release from glandular epithelial and stromal cells.

Animals↗

Evaluation of the anticonvulsant profile of progesterone in male amygdala-kindled rats.

While there is clinical evidence that progesterone has anticonvulsant activity in women with complex partial seizures, previous studies on the anticonvulsant effect of progesterone in experimental animal models are inconclusive. Moreover, the effect of progesterone on seizure parameters in fully amygdala-kindled rats which best resemble complex partial seizures has not been evaluated. Therefore, in the present work the anticonvulsant effect of progesterone at doses of 10, 30, 60 and 75 mg/kg in fully amygdala-kindled male rats was studied. Only at the high and sedative dose of 75 mg/kg, progesterone suppressed behavioral seizures and afterdischarges elicited 10 min after intraperitoneal (i.p.) administration. Pretreatment with the progesterone antagonist, 17beta-hydroxy-11beta-(4-dimethylaminophenyl)-17alpha-(prop- 1-ynyl)-estra-4,9-dien-3-one (RU 38486) at the dose of 3 mg/kg did not inhibit the anticonvulsant activity of progesterone, while pretreatment with the GABA(A) receptor antagonist, bicuculline (2 mg/kg) blocked the anticonvulsant effect of progesterone. Neither RU 38486 nor bicuculline had any effect on the seizure parameters. These findings suggest that only at large and sedative doses, progesterone has some anticonvulsant activity in male amygdala-kindled rats which may be partly mediated via the GABA(A) receptor complex interaction.

Amygdala↗

Anti-progesterones in obstetrics, ectopic pregnancies and gynaecological malignancy.

Table 2 summarizes the proven and potential uses of anti-progesterones in obstetrics and gynaecology. In addition to their role in the induction of menstruation and the interruption of first-trimester pregnancy, anti-progesterones can definitely accelerate cervical ripening and promote the termination of second-trimester pregnancy, especially in combination with exogenous prostaglandins. Furthermore, anti-progesterones can also initiate labour in the obstetric complication of fetal death in utero, leading to delivery of the fetus and placenta without additional medical treatment and without surgery in the majority of patients. The wider use of anti-progesterones for the induction of labour, with or without other adjuvants such as oxytocin or prostaglandin analogues, is still uncertain and awaits further study. Anti-progesterones may also be useful in the medical treatment of early ectopic pregnancy, either alone or in combination with other medicines. Preliminary results indicate that progesterone receptor antagonists may also be useful both for the initiation and promotion of lactation as well as the possible management of advanced breast cancer containing progesterone receptors. Finally, the usefulness of anti-progesterones in other gynaecological malignancies containing progesterone receptors, such as endometrial or ovarian cancers, awaits further study.

Animals↗

Effects of danazol and progesterone on sex hormone-binding globulin mRNA expression in human endometrial cancer cell line Ishikawa.

To ascertain one of the biological effects of danazol and progesterone on the uterine endometrial cancer cell line, Ishikawa, we investigated the effects of these steroids on sex hormone-binding globulin (SHBG) mRNA expression by competitive reverse transcription-polymerase chain reaction-Southern blot analysis (RT-PCR-SBA). Estradiol-17beta (E2) in any concentration given did not exert any significant effect on the expression of SHBG mRNA. Danazol and progesterone significantly (P < 0.05) suppressed the expression of SHBG mRNA dose-dependently starting at a concentration of 10(-6) and 10(-8) M, respectively. Progesterone, in a low concentration (10[-10] M) with E2 (10[-8] M), significantly (P < 0.05) increased the expression of SHBG mRNA, but danazol did not. In contrast, danazol and progesterone in high concentrations (10[-6] to 10[-5] M) with E2 (10[-8] M) significantly (P < 0.05) suppressed its expression. The time course study showed the time-dependent decrease of SHBG mRNA level by danazol and progesterone (10[-6] M) with or without E2 (10[-8] M), except for a temporal increase by progesterone. These findings suggest that danazol and progesterone in a superphysiological milieu down-regulate the intracellular SHBG-related steroidal actions, and that progesterone in a physiological milieu with estrogen up-regulates it in a hormone-dependent cell line. A decrease of intracellular SHBG caused by high-dose danazol or progesterone might partly contribute to the abolition of the intracellular estrogen-dominant milieu, and be related to the inhibition of estrogen-dependent growth of some endometrial cancer cells.

Adenocarcinoma↗

Progesterone up-regulates WT1 mRNA and protein, and alters the relative expression of WT1 transcripts in cultured endometrial stromal cells.

OBJECTIVE: To determine the change in expression of the Wilms tumor suppressor gene product, WT1, by progesterone alone in endometrial stromal cell culture and to study its relationship with prolactin, a marker of decidualization. In addition, to examine the change in ratio of WT1 isoforms with and without exon 5 message. METHODS: Endometrial biopsies were taken from eight patients who had hysterectomy. Stromal cells were isolated and cultured in the presence of progesterone alone (12 days) or progesterone and 8-bromo-cyclic adenosine monophosphate (cAMP) (6 days). RNA was extracted from cells, and reverse transcription, real-time polymerase chain reaction (PCR), and conventional PCR were done to analyze WT1 mRNA expression. Immunocytochemistry was performed on equivalent cells to study WT1 protein expression. Decidualization was identified by increased prolactin concentrations in the media and immunocytochemical markers IGFBP-1 and collagen IV. RESULTS: Reverse transcription and real-time PCR revealed a significant increase in WT1 mRNA with increasing progesterone concentrations when decidualization was occurring (n = 6, P =.002). Increasing progesterone concentrations also increased the proportion of the WT1 transcript containing a 17-amino-acid insert (+ exon 5 expression); changes in WT1 exon 5 expression have been shown to be involved in control of proliferation and differentiation. Significant correlations between WT1 message and prolactin existed at physiologic progesterone concentrations (6.25, 12.5, 25, and 50 nM; P <.05) until prolactin concentrations reached a plateau at 100 nM. At concentrations of progesterone alone (> 25 nM) and progesterone with 8-bromo-cAMP, WT1 protein was localized to the nuclei of many of the decidualized stromal cells. CONCLUSION: The changing expression of WT1 isoforms in endometrial stromal cells caused by progesterone may be important for differentiation into the decidualized phenotype.

8-Bromo Cyclic Adenosine Monophosphate↗

Role of estrogen and progesterone in the survival of ovarian tumors--a study of the human ovarian adenocarcinoma cell line OC-117-VGH.

BACKGROUND: The role of estrogen and progesterone in ovarian carcinogenesis and the growth and survival of ovarian cancer cells is controversial. In this study, we tested the effects of various concentrations of estrogen and progesterone on the survival of an ovarian cancer cell line. METHODS: The ovarian adenocarcinoma cell line, OC-117-VGH, is deficient in the following receptors: estrogen receptor (ER)alpha, ERbeta, and progesterone receptor (PR). Serial concentrations of estrogen and progesterone were used to evaluate the effects of estrogen and progesterone on the survival of ovarian cancer cells. The apoptosis-related genes Bcl-2 and Bax were used to check the possible mechanism of an estrogen or progesterone effect on survival of the cancer cell line. RESULTS: Estrogen 0.01-1.0 microM and progesterone 0.1-10.0 microM affected cell survival. As predicted, progesterone successfully downregulated anti-apoptotic Bcl-2 expression, and dose-dependently suppressed Bcl-2 expression in tumor cells. Paradoxically, estrogen showed the same effects. In addition, both hormones downregulated proapoptotic Bax expression. The net effect confirmed the role of downregulated Bcl-2 in reducing the survival of ovarian cancer cells. CONCLUSION: Based on the findings of decreased survival and/or growth in OC-117-VGH ovarian adenocarcinoma cells treated with either estrogen or progesterone, we suspect that both hormones act effectively against ER-negative and PR-negative ovarian cancer cells. These findings should lead to a reassessment of hormone therapy for ovarian cancers.

Adenocarcinoma↗

Molecular cloning, sequence analyses, and expression of complementary DNA encoding murine progesterone receptor.

Progesterone receptors exist in two molecular forms commonly designated as "A" and "B" forms, the relative proportion of which can vary among species. In murine tissues, progesterone receptor exists predominantly as the "A" form which, in mammary glands, is also under developmental regulation [Shyamala et al. (1990) Endocrinology 126, 2882-2889]. Therefore, toward resolving the molecular mechanisms responsible for the predominance of the "A" form of progesterone receptor in murine tissues and its developmental regulation, we have isolated, sequenced, and expressed the complementary DNA corresponding to the mouse progesterone receptor. Nucleotide sequence analysis revealed two in-frame ATG codons, such that the largest open reading frame beginning with the first codon could encode a polypeptide with an estimated molecular weight of 99,089, while the shorter open reading frame beginning with the second codon could produce a polypeptide with a calculated molecular weight of 81,829. The murine progesterone receptor had complete identity for the DNA binding domain of human and rabbit progesterone receptors and 99% homology with the chicken progesterone receptor; for the steroid binding domain, it had 96% homology with human and rabbit progesterone receptors and 86% homology with chicken progesterone receptors. Expression of the complete complementary DNA in Chinese hamster ovary cells yielded a protein which bound the synthetic progestin promegestone with an equilibrium dissociation constant of approximately 1 nM, and in Western blot analyses revealed both "A" and "B" forms of immunoreactive receptor.

Amino Acid Sequence↗

Concurrent inhibition of sexual behavior, but not brain [3H]estradiol uptake, by progesterone in female rats.

Chronic injections of high doses of progesterone (5 mg) and low doses of estradiol benzoate (EB; 2 microgram) resulted in less sexual behavior than did low doses of progesterone (.5 mg) and low doses of EB. In a typical procedure for inducing sexual behavior, EB and progesterone were given sequentially, separated by 42 hr. High levels of progesterone (2.5 and 5 mg) administered concurrently with EB inhibited the induction of sexual receptivity. Increasing the dose of EB from 2 microgram to 6 microgram or 10 microgram offset this inhibition. High doses of progesterone (5 mg) administered simultaneously or 2-16 hr prior to EB inhibited the induction of sexual behavior, but the inhibition waned when progesterone was administered 48 hr prior to EB. A single injection of progesterone (1 mg) that did not inhibit the induction of sexual behavior when administered concurrently with EB did inhibit lordosis when distributed into five injections (.2 mg) every 4 hr. The results of two experiments in which progesterone did not inhibit the uptake or retention of [3H]estradiol by brain cell nuclei suggest that the antiestrogenic action of progesterone in the central nervous system is not to interfere with the binding of estradiol.

Animals↗

Effect of progesterone on renal sodium handling in man: relation to aldosterone excretion and plasma renin activity.

1. The effect of progesterone on renal haemodynamics and intrarenal sodium handing was evaluated in thirteen normal men on a constant diet. Clearances were measured during maximal water diuresis and again 4-7 days later, this time 3 h after progesterone was given intramuscularly. Seven additional studies were performed 3 days after progesterone administration. Another four tests were performed on volunteers who had manifested renal 'escape' from the sodium-retaining effect of deoxycorticosterone acetate. 2. In acute progesterone studies glomerular filtration rate was unchanged, whereas effective renal plasma flow increased, so that filtration fraction decreased significantly. A similar in crease in urinary sodium occurred whether subjects received a low or high sodium diet. Indices which related to the distal delivery of filtrate (fractional urine flow and the sum of fractional free water and sodium clearances) increased significantly in both groups. The progesterone-induced increase in sodium excretion was not related to changes in plasma renin activity, renin substrate or urinary aldosterone. After 3 days of progesterone, the increase of sodium excretion was less than in the acute studies and urinary aldosterone increased tow- to four-fold. Progesterone failed to produce an acute increse in urinary sodium in subjects hyperexpanded by administration of exogenous mineralocorticoids. 3. Results suggest that the acute natriuretic action of progesterone is in part independent of aldosterone inhibition and that progesterone may inhibit sodium reabsorption at proximal as well as distal sites in the nephron.

Adult↗

Progesterone and 5 alpha-pregnane-3,20-dione in human amniotic fluid.

Progesterone and 5 alpha-pregnane-3,20-dione (5 alpha-DHP) were determined by radioimmunoassay in 242 amniotic fluid samples from 16-19 weeks of gestation. 165 samples fulfilled the criteria of the normal collective. There is a positive correlation (r = 0.359, p less than 0.001) between progesterone and 5 alpha-DHP. The mean concentration (+/- SD) of progesterone for normal pregnancies was 68.04 +/- 35.56 ng/ml, the mean for 5 alpha-DHP was 6.6 +/- 4.76 ng/ml. A slight decrease of the hormone concentrations with increase of the week of gestation was observed. 7 cases, who later developed EPH-gestosis showed a significant higher progesterone concentration (p less than 0.05). 16 women with premature labor had a significant higher 5 alpha-DHP concentration (p less than 0.05). Significantly elevated progesterone and 5 alpha-DHP values were found in 36 cases of bleedings in early pregnancy. Pregnant women older than 35 years proved to have a significant higher 5 alpha-DHP concentration (p less than 0.05). Also women, who delivered a child weighing less than 2,500 g (n = 8), showed a significant higher progesterone concentration (p less than 0.01). There was no difference in amniotic fluid progesterone and 5 alpha-DHP concentration depending on the sex of the child. The hormone concentrations of 3 cases with Morbus Langdon-Down were slightly below the mean concentration for progesterone and 5 alpha-DHP. Progesterone and 5 alpha-DHP concentrations were found to be normal in one case each of open Ductus Botalli, esophagial atresia, conjunctival bleeding with eyelid edema, teleangiectasia, Morbus Gaucher, sicklefoot, omphalocele, clubfoot, and stillbirth respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

5-alpha-Dihydroprogesterone↗