Antagonistic Effect Of Progesterone Research Articles

Steroid hormone signaling: multifaceted support of testicular function.

Embryonic development and adult physiology are dependent on the action of steroid hormones. In particular, the reproductive system is reliant on hormonal signaling to promote gonadal function and to ensure fertility. Here we will describe hormone receptor functions and their impacts on testicular function, focusing on a specific group of essential hormones: androgens, estrogens, progesterone, cortisol, and aldosterone. In addition to focusing on hormone receptor function and localization within the testis, we will highlight the effects of altered receptor signaling, including the consequences of reduced and excess signaling activity. These hormones act through various cellular pathways and receptor types, emphasizing the need for a multifaceted research approach to understand their critical roles in testicular function. Hormones exhibit intricate interactions with each other, as evidenced, for example, by the antagonistic effects of progesterone on mineralocorticoid receptors and cortisol's impact on androgens. In light of research findings in the field demonstrating an intricate interplay between hormones, a systems biology approach is crucial for a nuanced understanding of this complex hormonal network. This review can serve as a resource for further investigation into hormonal support of male reproductive health.

The chromatin landscape of the casein gene locus

For several decades, the regulation of casein gene expression by the lactogenic hormones, prolactin and glucocorticoids, has provided an excellent model system in which to study how steroid and peptide hormones regulate gene expression. Early studies of casein gene regulation defined conserved sequence elements in the 5' flanking region of these genes, including one of which was identified as a γ-interferon activation sequence (GAS). Although this site was thought to interact with a mammary gland-specific factor, purification and cloning of this factor by Bernd Groner and his colleagues revealed it was instead a new member of the signal transducers and activators of transcription family, Stat5, which was expressed in many tissues. The exquisite tissue-specific expression of the casein genes was subsequently shown to depend not on a single transcription factor but on composite response elements that interacted with a number of ubiquitous transcription factors in response to the combinatorial effects of peptide and steroid hormone signaling. More recent studies have defined cooperative effects of prolactin and glucocorticoids as well as antagonistic effects of progesterone on the chromatin structure of both the casein gene proximal promoter region as well as a distal enhancer. Local chromatin modifications as well as long-range interactions facilitated by DNA looping are required for the hormonal regulation of β-casein gene expression. The casein genes are part of a large gene cluster, and the chromatin landscape of the entire cluster is regulated in a tissue-specific and developmental manner. Finally, newly discovered large non coding RNAs, such as the pregnancy-induced non coding RNA (PINC) may play an important role in the epigenetic regulation of mammary gland differentiation.

Estrogen-induced calbindin-D 9k gene expression in the rat uterus during the estrous cycle: late antagonistic effect of progesterone.

Progesterone modulates estrogen-stimulated responses in the uterus. Calbindin-D 9k (CaBP9k), a 17 beta-estradiol-responsive gene expressed in the uterus, was used as a marker to examine the interactions between endogenous progesterone and estradiol in the rat. The variations in uterine CaBP9k messenger RNAs (mRNAs) during the rat estrous cycle indicated that CaBP9k gene expression was greatest during the estrogen-dominated phases (proestrus and estrus) and became totally repressed during diestrus, when progesterone predominates. Estradiol was found to be the major controlling factor of CaBP9k gene expression in vivo, progesterone antagonizing estrogen-induced CaBP9k gene expression. The inhibitory role of progesterone was further examined in two experiments. Mature cyclic rats were injected with the progesterone antagonist RU486 before the progesterone surge of proestrus, and the estrous cycle was mimicked in ovariectomized rats by sequential injections of estrogen and progestin. Progesterone did not appear to be involved in the rapid decrease in CaBP9k mRNA during estrus but was implicated in the down-regulation of the estrogen-stimulated CaBP9k gene expression at the end of estrus and during diestrus. This delayed effect of progesterone was confirmed in the ovariectomized rat model. CaBP9k mRNA accumulation in estrogen-primed ovariectomized rats was suppressed by estrogen followed 1 h later by the progesterone agonist R5020. This effect occurred more than 24 h after progestin treatment. The inhibition of the estrogen-induced CaBP9k gene expression in the rat uterus by progesterone is certainly mediated by the progesterone receptor, because progesterone had no effect without estrogen priming or when the antagonist RU486 was used. The delayed progesterone effect probably does not involve depletion of nuclear estrogen receptors, the major rapid mechanism proposed for estrogen inhibition by progesterone in the rodent uterus, or control of estrogen receptor synthesis, as shown by Northern blot analysis of estrogen receptor mRNA.

Estrogen-induced calbindin-D 9k gene expression in the rat uterus during the estrous cycle: late antagonistic effect of progesterone

Estrogen-induced calbindin-D 9k gene expression in the rat uterus during the estrous cycle: late antagonistic effect of progesterone

Progesterone and antiprogesterone (RU 38486) modulation of estrogen-inducible glycoprotein (USP-1) synthesis and secretion in rat uterine epithelial cells.

Previous study in this laboratory revealed that estrogen stimulates synthesis and secretion of 97K glycoprotein [uterine secretory protein-1 (USP-1)] in rat uterine epithelial cells. In the present communication, the effects of progesterone and antiprogesterone (RU 38486) on estrogen-stimulated USP-1 biosynthesis were investigated. Ovariectomized rats were treated with estrogen for 4 days to induce USP-1 synthesis and secretion. Then, progesterone and RU 38486 were injected sc. After 6 and 12 h of treatment, uterine luminal fluid proteins were labeled for 6 h by direct administration of [35S]methionine into uterine lumen. By radioimmune precipitation assay using specific antibody against USP-1, it was shown that progesterone can reduce the USP-1 synthesis and secretion, which were prestimulated by estrogen. This antagonistic effect of progesterone on estrogen-induced USP-1 biosynthesis was also evident by the decreased staining intensity of USP-1 in uterine epithelial cells, as revealed by the immunohistochemical method. Although RU 38486 itself did not manifest any effect on estrogen-stimulated USP-1 biosynthesis, it completely inhibited the progesterone-induced decrease in synthesis and secretion. This system is believed to provide a useful model to analyze the progesterone and antiprogesterone actions on rat uterine epithelial cells.

Anti-estrogens in fetal and newborn target tissues

The antagonistic effects of progesterone and of the anti-estrogens, tamoxifen and nafoxidine, to estrogen responses were studied in the target tissues of fetal and newborn guinea pigs. In the fetal uterus, progesterone inhibits the stimulatory effect provoked by estradiol on uterine growth, on progesterone receptor and on the acetylation of nuclear histones. Progesterone also blocks the synthesis of new progesterone receptor protein in organ culture. Tamoxifen or nafoxidine (1 or 10mg/kg/day injected to the mother for 3 days) provoke a uterotrophic effect similar to that of estradiol (1 mg/kg/day injected to the mother for 3 days) but these anti-estrogens have a limited effect on the progesterone receptor. Tamoxifen given together with estradiol antagonizes the effect of the estrogen on the acetylation of histones but the anti-estrogens do not block the effect of estradiol on uterine growth. Histological studies show that both estradiol and tamoxifen provoke a dramatic hypertrophie and hyperplastic effect particularly in the uterine epithelium. In the newborn uterus (6-day old), tamoxifen (s.c. injection of 0.6μg/g body weight) and estradiol (injection of 30 ng/g body weight) provoke a similar uterotrophic effect and both have a limited effect on the progesterone receptor. In the fetal thymus estradiol provokes a selective decrease in the larger and actively proliferating lymphoid cells of the cortical zone. Tamoxifen has a similar effect but to a much lesser extent than estradiol. On the other hand, tamoxifen antagonizes the effect of estradiol on this fetal tissue. It is concluded that during fetal life progesterone antagonizes the effect of estradiol but tamoxifen can act as an agonist or an antagonist of estrogen action which is a function of the type of response or organ considered.

Antagonistic effects of progesterone on estradiol-induced synthesis and degradation of uterine glucose-6-phosphate dehydrogenase.

Estradiol administered daily to ovariectomized mature rats stimulates uterine glucose-6-phosphate dehydrogenase (G6PD) to maximum levels within 72 h, a stimulation that is nearly 14-fold greater than the preinduced levels. Twice daily injections of progesterone given with daily estradiol injections caused the increases in G6PD activity to plateau prematurely after 36 h at levels that were 38% of the maximum estrogeninduced value at 72 h. The mechanisms of this delayed antagonistic effect of progesterone were determined by comparing the rates of uterine G6PD synthesis and degradation at various times during the 72-h response to estradiol in the presence and absence of progesterone. Progesterone first caused a significant reduction in the estradiol-induced rate of synthesis of uterine G6PD after a lag of 24 h, and the inhibition continued until 72 h, at which time rates of synthesis in animals treated with both hormones were only slightly above the rates in untreated controls. At 36 h, estradiol induced a 4...

Effect of exogenous estradiol-17β on plasma vitellogenin levels in male and female Chrysemys and its modulation by testosterone and progesterone

Injection of estradiol-17β into the freshwater turtle, Chrysemys picta induced hormone-specific and dose-dependent vitellogenic responses in both sexes. However, both the time course of induction and the magnitude of the responses showed marked sexual differences. No vitellogenin was detected in untreated males. Following a single injection of estradiol-17β (100 μg/100 g body wt) vitellogenin was first detected in the plasma 8 hr postinjection. Maximal levels (3.1 ± 0.8 mg/ml, n = 5) were obtained by Day 6. Multiple injections of estradiol-17β into males raised plasma vitellogenin levels to 10–20 mg/ml. The initial increases during the first 6 days post-hormone treatment were independent of the dose. Nonvitellogenic females have basal levels of 1–2 mg/ml vitellogenin in circulation. Female turles receiving equal amounts of estradiol-17β (100 μg/100 g body wt) as males demonstrated a response 10 times greater (32.6 ± 3.9 mg/ml, n = 5). Maximum levels were reached in 12–14 days. Multiple injections of the hormones brought plasma vitellogenin levels to concentrations attained during the natural vitellogenic season (40 mg/ml). When progesterone or testosterone were administered to male turtles in conjunction with estradiol-17β, both hormones inhibited the estrogen-induced vitellogenesis. The antagonistic effect of progesterone on estrogen was directly dose dependent; in contrast, the testosterone effect appeared to be inversely related to dose. Since both progesterone and testosterone concentrations reach high levels during the periovulatory phase of the gonadal cycle, it is suggested that these hormones may be of physiological significance in modulating vitellogenin level in the plasma.

Synergistic and antagonistic effects of progesterone and oestrogen on oestrogen receptor concentration and DNA polymerase activity in chick oviduct

Synergistic and antagonistic effects of progesterone and oestrogen on oestrogen receptor concentration and DNA polymerase activity in chick oviduct

A delayed antagonistic effect of progesterone on the estradiol-induced differentiation of the oviductal epithelium in spayed cats.

A delayed antagonistic effect of progesterone on the estradiol-induced differentiation of the oviductal epithelium in spayed cats was investigated. 2 groups of cats were treated wtih silastic implants of progesterone (12 cm) and estradiol (.5 cm) as follows: Group A: progesterone (7 days) progesterone plus estradiol (14 days). Oviducts were collected and fixed for morphologic and cytomorphometric determinations. Mean plasma levels of estradiol in Groups A and B were 16.8 and 19.7 pg/ml respectively. Mean plasma levels of progesterone were 14.1 ng/ml in Group A and .3 ng/ml in Group B. After 2 days of estradiol treatment cells from both treatment groups showed identical patterns of mitosis and hypertrophy On Days 3-5 combined treatment had prevented further cell hypertrophy but ciliogenesis was evident in cells from both groups. By Day 7 combined treatment had somewhat reduced the number of ciliated cells in the fimbriae (Group A 46% Group B 67%) and more dramatically in the ampulla (22 and 63% respectively). By 14 days combined treatment had led to further atrophy and extensive deciliation. The nonciliated cells never became functional secretory cells in the presence of progesterone. These results suggest that in cats a period of estradiol-induced differentiation must occur before progesterone can antagonize the estradiol effect that progesterone antagonism develops gradually and that the rate at which progesterone antagonism develops differs from 1 region of the oviduct to another.

Progesterone antagonism of aggression-promoting olfactory signals: A time-dependent phenomenon

Four experiments were conducted to test the possible antagonistic effect of progesterone (P) on androgen-dependent urinary signal output in mice. Experiment 1 showed that trained fighters did not react differentially to male castrates coated with aged urine collected from male castrates injected with testosterone propionate (TP) or TP+P. The failure of P's antagonism may be due to the storage of the urine. Experiments 2, 3, and 4 sought to clarify this possibility. In Experiment 2, fresh urine was used for testing. Results indicated that fighters behaved more aggressively to castrates coated with urine from TP injected donors than castrates coated with urine from TP+P donors. Experiments 3 and 4 were designed to test the hypothesis that aged TP+P urine was more aggression-promoting than fresh TP+P urine. Results confirmed the hypothesis.