Changes in cytosol and nuclear progesterone receptor concentrations in the rabbit uterus and their relation to induction of progesterone-regulated uteroglobin.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
V Isomaa
Publications and source records attributed to V Isomaa.
Regulation of cytosol and nuclear progesterone receptors in rabbit uterus by estrogen, antiestrogen and progesterone administration.
A synthetic progestin, 16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione (ORG 2058), was utilized to measure progesterone receptors from the rabbit uterus. This steroid has a high affinity for both cytosol and nuclear receptors, with KD values of 1.2 nM (at 0--4 degrees C) and 2.3 nM (at 15 degrees C), respectively. Administration of estradiol-17 beta or a non-steroidal antiestrogen, tamoxifen, for 5 days to estrous rabbits led to a progressive rise in the cytosol receptor levels: from 34,000 to 120,000 (estradiol-17 beta) and 80,000 (tamoxifen) receptors/cell, without any major influence on the nuclear receptor content. A single intravenous injection of progesterone (5 mg/kg) elicited a 3-fold increase in the mean nuclear receptor content at 30 min after injection (from 18,000 to 48,000 receptors/nucleus). Nuclear receptor accumulation was short-lived and returned to control levels within 4 h after treatment. A second dose of progesterone given 24 h later doubled the nuclear receptor level (from 18,000 to 35,000 receptors/nucleus). The concomitant decline in the cytosol receptor content was twice that accounted for by the nuclear receptor accumulation (70,000 vs. 30,000, and 40,000 vs. 17,000 receptors/cell, after the first and second progesterone injection, respectively). Following progesterone administration, the cytosol receptor level reached a nadir by 30 min, exhibited minimal replenishment within the ensuing 24 h, and remained at approx. 50% of the pretreatment values. After a single dose or two consecutive doses of progesterone, total uterine progesterone receptor content declined to about 60% of the level prior to each dose, a nadir being reached at 2 h after treatment.
Animals↗
Uterine estrogen and progestin receptors and their regulation.
Explore the source record for details and available documents.
Animals↗
Progesterone-regulated changes in transcriptional events in rabbit uterus.
The role of steroid receptors in the early events of progesterone action was elucidated by examining the temporal relationship between the nuclear accumulation of progestin receptor and changes in activities of RNA polymerases I and II, as well as that of chromatin template in rabbit uterus. Following a 5-day estrogen pretreatment, the animals received an intravenous injection of progesterone (10 mg), after which they were killed at timed intervals. Nuclear progestin receptor level, as measured by an exchange assay, reached the peak value 30 min after hormone administration (11 600 to 46 600 sites/nucleus) and declined to the control levels by 4 h. Changes in the activities of RNA polymerase I and II did not follow identical time courses: polymerase I rose at 30 min and remained elevated for 2 h and then declined to about 75% of the pretreatment activity, whereas RNA polymerase II activity increased more rapidly (at 15 min), and was followed by a sharp decrease to about 50% of the initial value. Thereafter, the latter enzyme activity rose slowly and reached the pretreatment level within 12 h of progesterone administration. Early changes in chromatin template activity were similar to those in RNA polymerase I with a second rise by 8--10 h. The early inhibition of transcriptional events by progesterone may result from antiestrogenic properties of this steroid. Accumulation of nuclear progestin receptor occurs at a similar time to early changes in the transcriptional events suggesting a regulatory role for the hormone receptor complexes.
Animals↗
Activin-A, but not inhibin, regulates 17beta-hydroxysteroid dehydrogenase type 1 activity and expression in cultured rat granulosa cells.
17beta-Hydroxysteroid dehydrogenase type 1 (17HSD type 1) catalyzes the reduction of estrone (E(1)) to biologically more active estradiol (E(2)). In the present study, the effect of activin, inhibin, and follistatin on 17HSD activity and 17HSD type 1 expression in cultured, unluteinized rat granulosa cells was examined. Furthermore, the effects of these hormones on 17HSD type 1 expression were compared with the expression of P450 aromatase (P450arom). Rat granulosa cells were pre-incubated in serum-free media for 3 days, followed by a 2-day treatment with activin, inhibin, follistatin and 8-Br-cAMP. Activin in increasing concentrations appeared to effect a dose-dependent increase in 17HSD activity. In addition, increasing concentrations of activin also increased 17HSD type 1 mRNA expression. Addition of 8-Br-cAMP at concentrations of 0.25 and 1.5 mmol/l together with activin significantly augmented the stimulatory effects of activin alone in the cultured cells. Neither inhibin, nor follistatin, either alone or in combination with 8-Br-cAMP, had any notable effects on 17HSD activity and 17HSD type 1 expression. Preincubation of activin with increasing concentrations of follistatin significantly diminished the stimulatory effect of activin. In the presence of follistatin, activin did not significantly increase the 8-Br-cAMP-induced 17HSD activity and 17HSD type 1 expression. The culturing of granulosa cells in the presence or the absence of inhibin or follistatin with or without 8-Br-cAMP did not alter the effect of these peptides on P450arom expression in rat granulosa cells as judged by Northern blot analysis of total RNA. However, cAMP-induced P450arom expression was enhanced by activin treatment, except when follistatin was present. This is in line with the suggested role of follistatin as an activin-binding protein, which limits the bioavailability of activin to its membrane receptors. Thus, the results support the notion of a paracrine/autocrine role of activin in follicular steroidogenesis of growing follicles.
8-Bromo Cyclic Adenosine Monophosphate↗