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At least 19 recordsLinked to original sources
PubMed1979

Serum levels of progesterone, 5 alpha-dihydroprogesterone and hydroxy-5 alpha-pregnanones in the prepartum and postpartum equine.

Blood samples were collected from eight mares for ten days before and two days following parturition. Progesterone, 5 alpha-dihydroprogesterone and hydroxy-5 alpha-pregnanones were extracted from serum, separated by Sephadex LH-20 column chromatography and quantitated by radioimmunoassay. Progesterone levels ranged from 8.5 to 4.1 ng/ml among mares with normal parturition and decreased to 1.2 ng/ml after parturition. One mare with a retained placenta maintained the prepartal levels of progesterone into the postpartum period. 5 alpha-dihydroprogesterone increased to a level of 133 ng/ml at 80 hrs before parturition and began decreasing and reached a level of 9.2 ng/ml in the postpartum period. Levels of hydroxy-5 alpha-pregnanones were variable with a high of 1690 ng/ml and declined to a postpartum level of 60 ng/ml. The timing of the decline varied among the mares. The possible source and significance of these progestins remain speculative.

20-alpha-Dihydroprogesterone↗
PubMed1991

Production of 5 alpha-dihydroprogesterone during late pregnancy in the mare.

Changes in the progesterone metabolite 5 alpha-dihydroprogesterone (5 alpha-DHP) in maternal plasma in late gestation, and possible sites of production of this steroid were studied in pony and Thoroughbred mares by an enzyme-linked immunosorbant assay for 5 alpha-DHP. In Thoroughbred mares, plasma 5 alpha-DHP increased from 63.7 +/- 10.5 ng/ml (27 days pre-partum) to 161.7 +/- 30.8 ng/ml (1 day pre-partum) falling to 90.2 +/- 16.1 ng/ml on the day of parturition. In pony mares, values rose from 30.8 +/- 8.1 ng/ml (27 days pre-partum) to 79.1 +/- 30.8 ng/ml (3 days pre-partum) and then decreased to 28.2 +/- 7.1 ng/ml on the day of parturition. Concentrations of 5 alpha-DHP were greater in the umbilical and uterine veins than in the corresponding umbilical and uterine artery samples. Tissues incubated with isotopically-labelled substrates showed that the fetal placenta converted pregnenolone to progesterone (47.5 +/- 9.0%). Endometrium metabolised [3H]pregnenolone to progesterone and 5 alpha-DHP (11.0 +/- 3.0% and 7.8 +/- 2.4%, respectively), and [14C]progesterone to 5 alpha-DHP (9.3 +/- 2.5%). Deuterium-labelled substrates were used to confirm the identity of these products by gas chromatography-mass spectrometry. Negligible amounts of 5 alpha-DHP were formed by other fetal tissues (adrenal, liver, kidney and testis). The results show that 5 alpha-DHP production in late pregnancy is derived primarily from endometrial metabolism of pregnenolone and/or progesterone.

5-alpha-Dihydroprogesterone↗
PubMed1979

Hormone production during pregnancy in the primigravid patient. I. Plasma levels of progesterone and 5-alpha-pregnane-3,20-dione throughout pregnancy of normal women and women who developed pregnancy-induced hypertension.

The plasma concentrations of progesterone and 5-alpha-pregnane-3,20-dione (5-alpha-dihydroprogesterone) were measured from as early as 12 weeks through 41 weeks of gestation in primigravid women. Two groups of primigravid women were assessed, those with uncomplicated pregnancies and those who developed pregnancy-induced hypertension. Plasma levels of progesterone and 5-alpha-dihydroprogesterone rose progressively throughout gestation in both groups of women. The ratio of the level of progesterone to that of 5-alpha-dihydroprogesterone in individual plasma samples of women with uncomplicated pregnancies was 7.0 from 12 to 15 weeks' gestation while at 35 to 41 weeks' gestation the ratio had declined to 4.6. Similar results were obtained in plasma samples of women who ultimately developed pregnancy-induced hypertension. Since no differences in plasma levels of progesterone or 5-alpha-dihydroprogesterone were detected between primigravid women with uncomplicated pregnancies and those who developed pregnancy-induced hypertension, we conclude that neither progesterone nor 5-alpha-dihydroprogesterone concentrations in plasma are of value in identifying women at risk of developing pregnancy-induced hypertension.

Female↗
PubMed1977

Effect of progesterone and its 5 alpha-reduced metabolites on gonadotropin levels in estrogen-primed ovariectomized rats.

In an effort to determine whether the metabolic conversion of progestrone may be important in the feedback effects of this steroid, serum LH and FSH levels were measured after administration of progesterone, 5 alpha-dihydroprogesterone or 3 alpha-hydroxy-5 alpha-pregnan-20-one to estrogen-primed ovariectomized rats. A single injection of 2 or 4 mg progesterone, 4 mg 5 alpha-dihydroprogesterone, or 4 mg 3 alpha-hydroxy-5 alpha-pregnan-20-one 72 h (Day 3) after estrogen pretreatment induced a highly significant increase in serum LH and FSH 6 h later (1800 h). Although serum gonadotropin levels had begun to decrease 12 h after administration of the progestins, they were still significantly higher than control values and did not return to baseline levels until noon on Day 4. When either progesterone or 3 alpha-hydroxy-5 alpha-pregnan-20-one was administered at noon on Days 3 and 4, there was a significant reduction in LH levels 6 h after the second injection. In contrast, serum LH levels were slightly elevated 3 to 6 h (1500 to 1800 h) after the second injection of 5 alpha-dihydroprogesterone and did not decrease until 2100 h. There was no effect on FSH concentrations after a second injection of any of the progestins. Loss of uterine luminal fluid was observed within 24 h after a single injection of progesterone. Neither of the 5 alpha-reduced metabolites had an effect on uterine ballooning until after the second injection, and, even then, nonfluid-filled uteri were observed in only 20 to 30% of the animals. The results suggest that the conversion of progesterone to 5 alpha-dihydroprogesterone and 3 alpha-hydroxy-5 alpha-pregnan-20-one by neuroendocrine tissues may be necessary for the positive and negative feedback effects of progesterone on gonadotropin secretion. Thus, the diverse effects of progesterone may be due to progesterone per se (e.g., in the uterus) and/or its metabolites (e.g., in the hypothalamus and pituitary).

5-alpha-Dihydroprogesterone↗
PubMed1979

Uptake and metabolism of female sex steroids by isolated small neurons and other cell fractions from the rat medial basal hypothalamus.

Rat medial basal hypothalami (MBH) and sections of cerebral cortex (CC) were dissociated with trypsin to prepare single cells and subcellular fractions. They were then separated into four fractions on a discontinuous sucrose gradient. The small neurons in Fraction D were highly purified. Fraction A had synaptosomes, myelin and other cell particulates. Fraction B had glial cells, neurons and a few synaptosomes. Fraction C had large neurons and red blood cells. All four fractions contained LHRH, but most (62.5%) of this hormone was present in Fraction A. Dissociated cell suspensions were incubated with [3H]-steroids, with and without a 100-fold excess of unlabeled steroids, then separated on sucrose gradients. In most fractions the total uptake and specific uptake of [3H]-progesterone, [3H]-5 alpha-pregnane-3,20-dione (5 alpha-dihydroprogesterone) and [3H]-17 beta-estradiol were greater for the dissociated cells from the MBH than the CC. The dissociated cells and cell particulates in all four fractions from the MBH and CC metabolized progesterone, 5 alpha-dihydroprogesterone and 17 beta-estradiol. These results indicate that hypothalamic neurons contain small amounts of LHRH and retain the ability to take up and metabolize progesterone, 5 alpha-dihydroprogesterone and 17 beta-estradiol.

20-alpha-Dihydroprogesterone↗
PubMed1990

Expression of cytochrome P-450(17) alpha, 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase, and steroid 5 alpha-reductase in rat H540 Leydig tumor cells.

The rat H540 Leydig tumor cell is established as a model for acute lutropin action on the initial step of steroidogenesis, namely the conversion of cholesterol to pregnenolone. Herein, we demonstrate that H540 cells express high levels of three steroid-metabolizing enzymes which are involved in the further processing of pregnenolone in the endoplasmic reticulum of the steroidogenic cell. In particular, in addition to expressing 17 alpha-hydroxylase cytochrome P-450 (P-450(17) alpha) and 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase (3 beta-HSD), H540 cells also showed high levels of steroid 5 alpha-reductase mRNA and activity. The H540 cells therefore exhibit similarity to Leydig cells from sexually immature animals which also demonstrate high 5 alpha-reductase activity. Thus, after 3 beta-HSD-catalyzed formation from pregnenolone, progesterone was efficiently converted to 5 alpha-pregnan-3,20-dione (5 alpha-dihydroprogesterone) and subsequent metabolism to the corresponding 17 alpha-hydroxylated derivative and 5 alpha-androstan-3,17-dione in a reaction catalyzed by P-450(17) alpha. H540 cells have apparently very low 17-ketosteroid reductase activity and, therefore, a principal end-product of the steroidogenic pathway in these cells was 5 alpha-androstan-3,17-dione. H540 cells maintained in primary culture under serum-free conditions accumulated demonstrable levels of mRNA species for P-540 17 alpha (1.7 kb), 3 beta-HSD (1.6 kb) and 5 alpha-reductase (2.7 kb). This finding suggests that the H540 tumor cell model will not only be of utility in the study of acute lutropin action but also in the elucidation of mechanisms involved in the regulation of expression of various families of microsomal steroid-metabolizing enzymes.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1978

Inhibitory effects of various progestins and deoxycorticosterone on the rapid onset of maternal behavior induced by ovariectomy-hysterectomy during late pregnancy in rats.

The inhibitory effects of progesterone (P), 5 alpha-dihydroprogesterone (5 alpha-DHP), 17 alpha-hydroxyprogesterone (17-HP), and deoxycorticosterone (DOC) upon the rapid onset of maternal behavior induced during late pregnancy in primigravid rats by ovariectomy-hysterectomy (OH) were examined. Progesterone administration at a dosage of 5.0 mg oil vehicle daily (beginning on Day 17 and ending when the subject responded maternally to foster pups) significantly delayed by about 1.5 to 2.0 days the onset of maternal behavior. In contrast, P at dosages of either 1.0 or 2.5 mg daily, 5 alpha-DHP at 5.0 mg administered daily in either an oil or Tween-80 vehicle, 17-HP at 5.0 mg in oil daily, and DOC at dosages of either 5.0 or 10.0 mg in oil daily failed to effect the rapid onset of maternal behavior induced by ovariectomy-hysterectomy on Day 17 of pregnancy. These data suggest that during pregnancy the onset of maternal behavior is inhibited in a rather specific manner by progesterone.

Algestone↗
PubMed1992

Role of 5 alpha-reduction in progesterone's ability to release FSH in estrogen-primed ovariectomized rats.

In ovariectomized estrogen-primed rats, progesterone as well as 5 alpha-dihydroprogesterone (5 alpha-DHP) are capable of inducing the release of gonadotropins. This study examined the need of 5 alpha-reduction as a prerequisite for the action of progesterone. The 5 alpha-reductase inhibitor, N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxamide was injected at a 1 or 2 mg dose/rat 2 h prior to an injection of 0.4 or 0.8 mg progesterone/kg body weight at 0900 h to immature ovariectomized, estrogen-primed rats and serum was analyzed for LH and FSH at 1500 h. Pituitary and hypothalamic 5 alpha-reductase activity was measured at the time of progesterone administration and at the time of the surge by incubating tissue homogenates with [3H]progesterone. Substrate, ([3H]progesterone) and product ([3H]5 alpha-DHP), were separated by reverse phase HPLC. The pituitary 5 alpha-reductase activity was not blocked at 1500 h. However, both pituitary and hypothalamic 5 alpha-reductase was blocked at the time of progesterone administration. No effect was seen by acute administration of the 5 alpha-reductase inhibitor upon either the 0.4 or 0.8 mg progesterone/kg-induced release of LH and FSH. There was, however, a specific, significant inhibition of progesterone-induced FSH but not LH release when the 5 alpha-reductase inhibition was sustained throughout the afternoon of the gonadotropin surge. These results indicate a biologically significant role for the irreversible 5 alpha-reduction of progesterone in the modulation of the release of FSH.

Androgen Antagonists↗
PubMed1992

Pituitary progestin-metabolizing enzyme activities in the aged female rat.

Progesterone 5 alpha-reductase activity and 5 alpha-dihydroprogesterone 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR) enzymic activities (NADH-linked and NADPH-linked) were measured in anterior pituitaries (AP) from aged female rats during three stages of reproductive senescence (constant estrus: CE; repeated pseudopregnancies: PSP; and anestrus: AN). To assess ovarian influence on these enzymes during these stages of reproductive aging, we also determined enzyme levels from ovariectomized rats from each stage treated with estrogen or vehicle. Progesterone 5 alpha-reductase and NADH-linked 3 alpha-HSOR activities were 2-fold higher in pituitaries of CE rats as compared to those of PSP and AN rats. NADPH-linked 3 alpha-HSOR levels did not differ among the three stages. All three enzyme levels were elevated 2- to 5-fold as compared to the corresponding enzyme levels from young cycling rats. After ovariectomy (10 days), 5 alpha-reductase activity in PSP and AN rats was elevated 3- to 4-fold relative to mean levels in intact PSP and AN rats. Ovariectomy had no effect on 5 alpha-reductase levels in CE rats. Under similar conditions, young cycling rats exhibit a 10-12-fold increase. Treatment of ovariectomized PSP and AN rats for 3 days with estradiol benzoate (10 micrograms/day) restored 5 alpha-reductase levels. Ovariectomy had no effect on the NADPH-linked 3 alpha-HSOR levels in CE, PSP or AN animals which is similar to that observed with young rats. Ovariectomy also had no effect on the NADH-linked 3 alpha-HSOR levels except for the CE group. The ovariectomized CE rats exhibited reduced pituitary NADH-linked 3 alpha-HSOR levels (30%). In contrast, young rats exhibit elevated pituitary NADH-linked 3 alpha-HSOR levels after ovariectomy (4- to 5-fold). These changes suggest the possibility that altered processing of progesterone and its 5 alpha- and 3 alpha-reduced products may be one means by which the effectiveness of progesterone is reduced during aging. The results also suggest an altered ovarian role in the regulation of these enzymes.

3-Hydroxysteroid Dehydrogenases↗
PubMed1979

Progesterone receptor in the hypothalamic cytosol of female rats.

A progesterone (P)-binding component with a sedimentation coefficient of 8S has been demonstrated in hypothalamic cytosol from ovariectomized, estrogen-primed rats using both [H]P-containing sucrose-glycerol gradient analysis and dextran-coated charcoal adsorption of the preisolated 8S component. The association rate constant (K+1) was determined to be 1.90 +/- 0.38 (SD) X 10(6) M-1 min-1 at 0-2 C. The dissociation rate constant (K-1) was 1.86 x 10(-2) min-1, as calculated from the half-dissociation time [37.0 +/- 7.3 (SD) min]. The apparent dissociation constant (Kd) at 0-2 C was determined to be 6-10 nM by Scatchard plot analysis of data obtained from either direct [3HA]P binding or competition of the [3H]P binding by nonradioactive P and by calculating from K-1/K+1. The 8S binding component was protein in nature, and the concentration of binding sites was 12 fmol/mg cytosol protein. On a per U cytosol protein basis, the relative capacities of the specific 8S binding components were: uterus greater than pituitary greater than hypothalamus greater than hippocampus/amygdala greater than cerebral cortex. Competition studies showed a high specificity for P and 5 alpha-dihydroprogesterone. Corticosterone (C), although competing for the binding, had an affinity 8-fold less than P. Implantation of C in adrenalectomized, ovariectomized, estrogen-implanted rats suppressed the 8S binding of [3H]C without affecting the [3H]P binding. The binding of [3H]P to the cytoplasmic 8S component of hypothalamus was greater than that of combined hippocampus and amygdala, while the reverse was observed for the binding of [3H]dexamethasone. These results demonstrate in rat hypothalamic cytosol a tissue and hormone-specific, high affinity, 8S progesterone-binding protein which has many of the properties expected of a hormone receptor.

Animals↗
PubMed1992

General anesthetics potentiate gamma-aminobutyric acid actions on gamma-aminobutyric acidA receptors expressed by Xenopus oocytes: lack of involvement of intracellular calcium.

Potentiation of the gamma-aminobutyric acid (GABAA) receptor-gated Cl- channel response has been suggested to be a primary action of some anesthetic agents. We asked whether the GABAA receptor is a target site common for general anesthetics that are chemically and structurally diverse. This hypothesis was tested in Xenopus oocytes expressing mouse cortical mRNA, and GABA-activated Cl- currents were measured using two-electrode voltage clamping. General anesthetics, including inhalational (halothane, diethylether, enflurane and isoflurane), i.v. (3 alpha-hydroxy-5 alpha-dihydroprogesterone, ketamine and propofol) and alcohol (pentanol) anesthetics, enhanced GABA-induced currents by 56 to 1089% at concentrations that were clinically relevant. The results suggest that potentiation of the GABAA receptor/channel response may be a common action for anesthetic agents. Moreover, anesthetic effects were dependent on GABA concentrations; the enhancement was marked with low GABA concentrations and was exponentially decreased as the GABA concentration increased. Also, anesthetic effects were dependent on anesthetic concentrations. The apparent EC50 of halothane was found to be similar to the anesthetic ED50. We also investigated the role of intracellular Ca++ in mediating anesthetic enhancement of the GABA current. We found that intracellular injection of the Ca++ chelator, EGTA, did not change the enhancement by anesthetics. In addition, these anesthetics alone did not produce significant currents, suggesting that the Ca(++)-dependent Cl- current was not activated by these anesthetics per se. Thus, we found that diverse anesthetics potentiate GABA-induced Cl- currents, but this action is not mediated by a release of intracellular Ca++.

20-alpha-Dihydroprogesterone↗
PubMed1992

Testosterone and 5 alpha-dihydrotestosterone interact differently with the androgen receptor to enhance transcription of the MMTV-CAT reporter gene.

Testosterone and its 5 alpha-reduced derivative 5 alpha-dihydrotestosterone exert different actions in the male during embryogenesis and in postnatal life. Nevertheless the two hormones bind to the same intracellular androgen receptor, and genetic and endocrinological studies in the Tfm mouse suggest that the actions of both hormones are mediated by this single receptor. Previous studies indicate that dihydrotestosterone binds more tightly to the androgen receptor but that the Bmax of binding of the two hormones is the same. To determine whether these differences in binding parameters could explain the mechanism by which the two hormones exert different physiological actions via the same receptor, we introduced a plasmid encoding the androgen receptor cDNA and a reporter plasmid encoding MMTV-CAT into Chinese hamster ovary cells. These cells do not express endogenous androgen receptor and do not convert testosterone to dihydrotestosterone. Therefore, it was possible to examine the relation between the concentration of each of the steroids and reporter gene expression. Both hormones enhanced CAT activity, but dihydrotestosterone was approximately 10 times as potent (half maximal of 0.018 nM) as testosterone (half maximal of 0.2 nM); the maximal activity achieved was the same for the two androgens. These findings are nearly identical to the apparent Kd values for the interaction of the two hormones with the androgen receptor. Although testosterone and dihydrotestosterone may influence the expression of other genes differently, these findings are compatible with a model system in which the differential effects can be explained as a consequence of different binding affinities to the receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

5-alpha-Dihydroprogesterone↗
PubMed1992

Evidence that 3 alpha-hydroxy-5 alpha-pregnan-20-one is the metabolite responsible for anesthesia induced by 5 alpha-pregnanedione in the mouse.

Mice were anesthetized with [3H]5 alpha-pregnanedione (5 alpha). Brain levels for 5 alpha and its metabolites were quantitated and compared at time points following injection and at two behavioral endpoints that are characteristic of the anesthetized state. The results support the hypothesis that 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha), a metabolite of 5 alpha, mediates this anesthetic response, and they weigh against the hypothesis that 5 alpha itself is solely responsible for activity. Anesthesia occurred at 3-8 min following injection. During this period, levels of 3 alpha derived from 5 alpha were comparable to those seen when 3 alpha was administered alone. It is estimated that 5 alpha, if active at all, is at least 3-5 times less potent than 3 alpha.

5-alpha-Dihydroprogesterone↗
PubMed1991

Inhibition of uterine contractility by progesterone and progesterone metabolites: mediation by progesterone and gamma amino butyric acidA receptor systems.

Progesterone and several progesterone metabolites are capable of inhibiting uterine contractility. Some progesterone metabolites have shown little or no affinity for the progesterone receptor but have been found to be potent modulators of the GABAA receptor system. This study examined whether the inhibition of uterine contraction by progesterone and its metabolites was progesterone receptor-mediated or gamma amino butyric acidA (GABAA) receptor-mediated. Uterine contractions were measured in annular rings of uterine tissue, 5 mm in length, from diestrous II rats, under a fixed tension of 1 gram. The steroids tested were 3 beta-hydroxy-5 beta-pregnan-20-one (6 micrograms/ml), 5 beta-pregnane-3,20-dione (10 micrograms/ml), 3 alpha-hydroxy-5 alpha-pregnan- 20-one (3 alpha,5 alpha-THP, 27.5 micrograms/ml), and progesterone (40 micrograms/ml). All compounds significantly inhibited spontaneous uterine contractions when compared to controls. No effect was seen by either 16 micrograms/ml of the progesterone antagonist, RU486, or 32 micrograms/ml of the GABAA antagonist, pictrotoxin, when administered alone. However, when uterine tissues were exposed to a combination of the steroid and the antagonist, the effect of 3 beta-hydroxy-5 beta-pregnan-20-one and 3 alpha,5 alpha-THP was blocked by picrotoxin but not by RU486, indicating that the action of these steroids was mediated through the GABAA system. The effect of 5 beta-pregnane-3,20-dione and progesterone was effectively blocked by RU486 but not by picrotoxin, suggesting that their actions were mediated through the progesterone receptor system. These results indicate that multiple mechanisms exist in the uterus for inhibiting uterine contractility by progesterone and its metabolites.

5-alpha-Dihydroprogesterone↗
PubMed1991

In vivo studies identify 5 alpha-pregnan-3 alpha-ol-20-one as an active anesthetic agent.

Mice were anesthetized with 5 alpha-[3H]pregnan-3 alpha-ol-20-one. Brain levels for 5 alpha-pregnan-3 alpha-ol-20-one and its five major metabolites (5 alpha-pregnanedione, k0, k1, k2, k3) were compared at behavioral endpoints that are characteristic of the anesthetized state. The results support the hypothesis that 5 alpha-pregnan-3 alpha-ol-20-one mediates the anesthetic response, and they weigh against the hypothesis that any of its metabolites is solely responsible for the onset or the maintenance of the anesthetized state. For an administered dose of 3 mg/kg, brain levels (means +/- SEM) for 5 alpha-pregnan-3 alpha-ol-20-one at the time of the loss of the righting response (n = 10) and at the time of the return of the righting response (n = 6) were 7.24 +/- 0.61 pmol/mg of brain tissue and 3.63 +/- 0.26 pmol/mg of brain tissue, respectively. No metabolite level was lower at the return of the righting response than at the loss of the righting response. 5 alpha-Pregnan-3 alpha-ol-20-one brain levels increased consistently with the percentage of anesthetized mice. This was not the case for any of the metabolites. Fifty percent of the mice were anesthetized when the 5 alpha-pregnan-3 alpha-ol-20-one level was 4.5 pmol/mg of brain tissue.

5-alpha-Dihydroprogesterone↗
PubMed1991

Altered tissue metabolism of progesterone in pregnancy gingivitis and granuloma.

The metabolism of progesterone may play a special role in the gingival physiology. The lower the metabolism the higher its hormonal activity in the tissue. In healthy human gingiva, progesterone is metabolized only partially and is therefore in an active form. In the present study, gingival samples from pregnancy gingivitis (n = 1) and granulomas (n = 4) were studied histologically and biochemically. All samples were homogenized and then incubated with [4-14C]-progesterone and NADPH for 2 h at pH 7.4 and 37 degrees C. The metabolites were separated and characterized with column, solvent and thin-layer chromatographies as well as radioautography and quantified with liquid scintillation counting. The results showed low metabolism of progesterone, indicating active hormonal function as in healthy gingiva. It is suggested that progesterone functions as an immunosuppressant in the gingival tissues of pregnant women, preventing the rapid acute-type of inflammatory reaction against plaque, but allowing an increased chronic-type of tissue reaction, resulting clinically in an exaggerated appearance of inflammation.

5-alpha-Dihydroprogesterone↗