Prostaglandins in the uterus: modulation by steroid hormones

Phospholipase A2 (PLA2), one of the enzymes considered to be rate-limiting in generating free arachidonic acid for prostaglandin (PG) synthesis, endogenous concentrations and in vitro production of PGs in the rat uterus were studied under various experimental conditions. Uterine PLA2 activity showed a 167-fold increase in ovariectomized rats bearing estradiol-17 beta (E2)-implants as compared to those treated with vehicle only. On the other hand, dexamethasone treatment reduced the E2-stimulable PLA2 activity by about 24-fold. The uterine PLA2 activity in the ovariectomized rat uterus was low and not altered by instillation of progesterone (P4) implants or by administration of dexamethasone. On the contrary, simultaneous placement of E2- and P4-implants prevented significantly the rise in PLA2 activity as observed under unopposed E2 exposure. Dexamethasone treatment further reduced the activity. The endogenous concentration of uterine PGF was several fold higher in the E2-implanted ovariectomized rats as compared to those without the E2-implants or carrying only P4-implants. The simultaneous treatment of the E2-implanted rats with P4 and/or dexamethasone reduced the uterine PGF concentrations considerably. The uterine PGF concentration was always lower in the ovariectomized rats under any condition if they were not treated with E2. Uterine PGE-A concentration did not change significantly between the ovariectomized rats and the ovariectomized rats carrying E2-implants. The treatment with P4 and/or dexamethasone, however, tended to decrease the PGE-A concentration. The production of PGF by the uterine homogenate increased by several fold in ovariectomized rats implanted with E2-silastic capsules as compared to those without the E2 implants. The treatments of the E2-implanted rats with P4 or dexamethasone did not alter this production. However, simultaneous exposure of E2-implanted rats to P4 and dexamethasone lowered the production rate of PGF in the uterus. The treatment of the ovariectomized rats with dexamethasone of P4 tended to elevate the uterine PGF production. The uterine PGE-A production followed more or less the same pattern. The analysis of our present data suggests that although a relationship exists between uterine PLA2 activity and PGF concentration, the role of PG synthetase could also be important in regulating PGF synthesis. Our study with dexamethasone, which showed inhibition of uterine PLA2 activity and decline in endogenous but not in vitro production of PGs, indicate that cellular integrity is essential for PLA2 to function as a rate-limiting step in PG synthesis.(ABSTRACT TRUNCATED AT 400 WORDS)     

Modulation of antioxidant enzyme activities by sexual steroid hormones

Taking into consideration the biological importance of interaction between antioxidant defense (AD) enzymes and sexual steroid hormones it was deemed important to compare our recent achievements in the field with the state of current knowledge. The main goal of the present review was to investigate the changes of AD enzyme activities: superoxide dismutases, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase in the brain of female and male rats depending on progesterone and estradiol. These ovarian steroids produce their effects by acting on numerous target tissues and organs, such as the reproductive organs, bone tissue and cartilage, peripheral blood vessels and the central nervous system (CNS). We have chosen it as a new parameter that might represent an important indicator of the changes within the CNS, bearing in mind the biological importance of the enzymes of the AD system. Our experimental results indicate that the AD enzyme activities in the brain tissue of female and male rats show a certain dependence on the concentration of progesterone and estradiol. The present review suggests that the modulation of the oxidative and antioxidative capacity by sexual steroid hormones is mediated through antioxidant metabolizing enzymes.     

Attenuated hypotensive response to proadrenomedullin N-terminal 20 peptide in pregnant rats: modulation by steroid hormones

The hypotensive effect of proadrenomedullin N-terminal 20 peptide (PAMP) was examined in conscious pregnant (8, 14, and 20 days of pregnancy) and nonpregnant rats. Intravenous administration of PAMP (3–60 nmol/kg) produced a dose-dependent depressor response in both pregnant and nonpregnant rats. However, the maximum decrease in blood pressure was significantly attenuated in pregnant rats in mid- and late-gestation (14 and 20 days), but not in early gestation (8 days), than in nonpregnant rats. In ovariectomized rats, the depressor responses in 17β-estradiol (E2)-treated, progesterone (P)-treated, and E2+P-treated rats were significantly attenuated compared with the control rats. We also demonstrated that treatment of sex hormones reduces the depressor response to PAMP in 8-day pregnant rats. In addition, we showed that treatment of sex hormone receptor antagonists partially prevents the attenuation of the depressor response to PAMP in 20 day pregnant rats. These findings suggested that the hypotensive response to PAMP was more attenuated in pregnant rats in mid- and late-gestation than in nonpregnant rats, and that the changes in depressor response that occur at term in pregnant rats may be mediated by sex hormones. PAMP may play some important role in cardiovascular regulation during pregnancy.     

Modulation of short term and long term memory by steroid sexual hormones

Many studies have evidenced a functional interrelation between the nervous and endocrine systems in the modulation of mnemonic processes, and others have established the role played by certain hormones in these processes; however, few studies have dealt with the effects of sexual steroids on learning and memory. The aim of this work was to determine whether shortterm and long-term memory is subject to hormonal modulation. Male Wistar rats, randomly assigned to 13 groups, 1 control and 12 experimental groups, were trained on a one-trial passive avoidance conditioning. The control group received saline solution, and each of the 12 experimental groups received a treatment consisted in one of following pharmacological doses of: 5, 10, 20, 30 mg of testosterone enanthate, 0.2, 0.4, 0.8, 1.2 mg estradiol valeriate, or 1, 2, 4, 6 mg norandrostenolone decanoate, respectively. All substances were applied 45 min before the training session. Retention of the learned response was tested 10 min (short-term memory) and 24 h (longterm memory) after the training session. Results indicate that under these experimental conditions the short-term memory is facilitated with testosterone enanthate at doses of 20 and 30 mg, the estradiol valeriate at doses of 0.4 mg and the nor-androstenolone decanoate at doses of 4 mg, whereas the long-term memory is facilitated with testosterone enanthate at doses of 30 mg, estradiol valeriate at doses of 1.2 mg and the nor-androstenolone decanoate at doses of 4 mg. The other studied doses were no effective.     

Reciprocal modulation by sex steroid and calciotrophic hormones of skeletal cell proliferation

We have demonstrated previously that 17 beta-estradiol (E2) stimulates cell proliferation in skeletal tissues, as measured by increased DNA synthesis and creatine kinase (CK) specific activity, and that calciotrophic hormones modulate E2 activity in rat osteoblastic sarcoma cells (ROS 17/2.8). Moreover, E2 failed to stimulate DNA synthesis in vitamin D-depleted female rat bone in the absence of prior i.p. injections of 1.25(OH)2D3. We have, therefore, studied the effects of pretreatment of cells by one hormone on their response to challenge by a second hormone. We now report reciprocal interactions of sex steroids and other hormones modulating bone formation on cell proliferation parameters in primary bone and cartilage cell cultures: these interactions can selectively augment or diminish cell responsiveness to a given hormone. Pretreatment of rat epiphyseal cartilage cell cultures with 1.25(OH)2D3, 24.25(OH)2D3 or parathyroid hormone (PTH) for 5 days, followed by E2 treatment for 24h, resulted in increased DNA synthesis compared to cultures pretreated with vehicle. Prostaglandin (PGE2) pretreatment blocked further response to E2. In the reciprocal case, rat epiphyseal cartilage cells, pretreated with E2, showed an increased response to PTH, a loss of the response to PGE2 or 24.25(OH)2D3 and an inhibition of CK activity and DNA synthesis by 1.25(OH)2D3, similar to the characteristic inhibitory action of 1.25(OH)2D3 in osteoblasts. By contrast, rat epiphyseal cartilage cells pretreated with testosterone showed no changes in response to PTH, 24.25(OH)2D3 or PGE2 and a decreased response to E2, but were stimulated by 1.25(OH)2D3. Rat embryo calvaria cell cultures behaved similarly to epiphyseal cartilage cultures except that 24.25(OH)2D3 pretreatment did not increase the response to E2. Reciprocally, pretreatment with E2 before exposure to calciotrophic hormones did not change the responses of rat embryo calvaria cell cultures to 1.25(OH)2D3 or 24.25(OH)2D3. These findings suggest that the mutual interactions between calciotrophic hormones and E2, demonstrated here in vitro, could selectively affect the responses of bone and cartilage cells to E2 by several mechanisms. These possibilities include increased E2 receptors and E2-stimulated differentiation of cartilage cells to more E2 responsive cells showing some characteristics of osteoblasts.     

Excitatory amino acid regulation of gonadotropin secretion: modulation by steroid hormones

Excitatory amino acids (EAAs) can potently modulate gonadotropin secretion in the male rat and monkey. In the present study we examined of EAAs on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the female rat under low estrogen (ovariectomized) and high estrogen (proestrus) backgrounds. In ovariectomized immature female rats (NMDA) inhibited LH but not FSH secretion at 30 min post-injection. In contrast, NMDA potently stimulated LH but not FSH secretion when administered on proestrus to adult female rats. Both glutamate and kainate were also found to stimulate LH but not FSH secretion in estrogen-treated ovariectomized immature rats. This study suggests that EAA neurotransmission may be an important component in the expression of gonadotropin surges and that EAA effects appear to be subject to gonadal steroid regulation.     

Hormonal modulation of food intake in response to low leptin levels induced by hypergravity

A loss in fat mass is a common response to centrifugation and it results in low circulating leptin concentrations. However, rats adapted to hypergravity are euphagic. The focus of this study was to examine leptin and other peripheral signals of energy balance in the presence of a hypergravity-induced loss of fat mass and euphagia. Male Sprague-Dawley rats were centrifuged for 14 days at gravity levels of 1.25, 1.5, or 2 G, or they remained stationary at 1 G. Urinary catecholamines, urinary corticosterone, food intake, and body mass were measured on Days 11 to 14. Plasma hormones and epididymal fat pad mass were measured on Day 14. Mean body mass of the 1.25, 1.5, and 2 G groups were significantly (P < 0.05) lower than controls, and no differences were found in food intake (g/day/100 g body mass) between the hypergravity groups and controls. Epididymal fat mass was 14%, 14%, and 21% lower than controls in the 1.25, 1.5, and 2.0 G groups, respectively. Plasma leptin was significantly reduced from controls by 46%, 45%, and 65% in the 1.25, 1.5, and 2 G groups, respectively. Plasma insulin was significantly lower in the 1.25, 1.5, and 2.0 G groups than controls by 35%, 38%, and 33%. No differences were found between controls and hypergravity groups in urinary corticosterone. Mean urinary epinephrine was significantly higher in the 1.5 and 2.0 G groups than in controls. Mean urinary norepinephrine was significantly higher in the 1.25, 1.5 and 2.0 G groups than in controls. Significant correlations were found between G load and body mass, fat mass, leptin, urinary epinephrine, and norepinephrine. During hypergravity exposure, maintenance of food intake is the result of a complex relationship between multiple pathways, which abates the importance of leptin as a primary signal.     

Hormonal influence on rat vas deferens responses induced by field stimulation

The effect of castration and treatment with testosterone propionate (PT), estradiol benzoate (E2) and ciproterone acetate (CPA) on the responses of the vas deferens in rat has been studied. Castration produces a time-dependent decrease of the response amplitude. PT augments the response amplitude in normal rats and reverses the effect of castration. E2 augments the response amplitude in normal rats without modifying the castration effect. CPA does not change the response of the vas deferens. The results suggest that PT and E2 through possible different mechanisms, facilitate the transmission in rate vas deferens, whereas castration obstructs it.     

Effects of acute unilateral ovariectomy to pre-pubertal rats on steroid hormones secretion and compensatory ovarian responses

In the present study we analyzed the existence of asymmetry in the secretion of steroid hormones in pre-pubertal female rats treated with unilateral ovariectomy (ULO) or unilateral perforation of the abdominal wall (sham-surgery). Treated rats were sacrificed at different times after surgery. Since sham-surgery had an apparent effect on the age of first vaginal estrous (FVE) and serum levels hormone, the results of the sham surgery groups were used to assess the effects of their respective surgery treatment groups. On the day of FVE, compensatory ovulation (CO) and compensatory ovarian hypertrophy (COH) were similar in animals with ULO, regardless of the ovary remaining in situ. In ULO treated animals, progesterone (P4) levels were higher than in animals with sham-surgery one hour after treatment but lower in rats sacrificed at FEV. Left-ULO resulted in lower testosterone (T) concentration 48 and 72 hours after surgery. In rats with Right-ULO lower T concentrations were observed in rats sacrificed one or 72 hours after surgery, and at FVE. ULO (left or right) resulted in lower estradiol (E2) concentrations one or 72 hours after treatment. In rats with Left-ULO, E2 levels were higher 48 hours after surgery and at FVE. Left-ULO resulted in higher levels of follicle stimulating hormone (FSH) five hours after surgery and at FVE. FSH levels were higher in rats with Right-ULO sacrificed on FVE. The present results suggest that in the pre-pubertal rat both ovaries have similar capacities to secrete P4, and that the right ovary has a higher capacity to secrete E2. Taken together, the present results support the idea that the effects of ULO result from the decrease in glandular tissue and changes in the neural information arising from the ovary.     

Regulation of apoptosis by steroid hormones

Steroid hormones play major roles in regulation of growth, development, homeostasis, and cell death. Together with other hormones and growth factors, steroids regulate both the function and cellular composition of organs throughout the body. In this article we will discuss the mechanisms of steroid hormone regulated apoptosis. Emphasis will be placed on the effect of glucocorticoids on lymphoid cells.     

Effects of sexual steroid hormones on the functionality of murine peritoneal macrophages.

In the present work, we studied the possible effect of steroid hormones, estradiol, progesterone, and 5 alpha-dihydrotestosterone, on different phenotypic and functional characteristics of peritoneal adherent mononuclear cells. We used female and male mice of Balb/c strain, normal, gonadectomized, and gonadectomized with hormonal replacement. We found that gonadectomy in both sexes produced a significant decrease in the functionality of membrane receptors for the complement and in phagocytic activity of Candida albicans-anti-C albicans system. In addition, the percentages of cells that reduced nitroblue tetrazolium were diminished in castrated animals. Ovariectomized females injected with estradiol presented normal levels of phagocytic and metabolic capacities, but the expression of membrane receptors for complement remained decreased. In contrast, progesterone treatment of ovariectomized animals had the opposite effect. Simultaneous treatment with estradiol plus progesterone gave results similar to those observed with estradiol only. Dihydrotestosterone per se did not affect any of the parameters measured in the conditions used here. These results suggest that female steroids affect macrophage functionality, probably by regulating surface receptors that are involved in phagocytic activity.