Estrogenic influence on the regulation of hepatic estrogen receptor-alpha and serum level of angiotensinogen in female rats

The majority of data regarding biological effects of estrogens is based on studies in male rats or ovariectomized (Ovx) female rats. Therefore, in this study, the effects of estradiol treatment on the regulation of the hepatic estrogen receptor and the level of circulating angiotensinogen were examined in the intact female rat. The data were compared with that of the hypophysectomized (Hx) rat. Animals were treated with either low (physiological) or high (pharmacological) doses of estrogen. In intact rats, the hepatic estrogen receptor (ER) level increased with increasing doses of estrogen. This was in contrast to the Hx rats where growth hormone (GH) and dexametasone (Dex) in combination were the sole modulators of the estrogen receptor. The angiotensinogen level increased in normal rats after estrogen administration in a dose dependent manner, regardless of the mode of administration. The pure antiestrogen ICI 182 780 efficiently blocked the increase in circulating angiotensinogen. The conclusion is that in the normal female, estrogens are important modulators of the serum angiotensinogen level.     

Induction of lordosis in female rats: two modes of estrogen action and the effect of adrenalectomy.

In ovariectomized female rats, progesterone treatment alone does not induce lordosis, but following estrogen treatment by an appropriate interval it greatly enhances the performance of lordosis compared to that with estrogen alone. This “facilitating” effect of progesterone is thought to act synergistically with the initial “priming” effect of estrogen. In the present experiments a second estrogen treatment given to estrogen-primed ovariectomized rats in place of progesterone was found to facilitate lordosis. Latency of the facilitation of lordosis following this second estrogen treatment was similar to that of progesterone and was much shorter than that required for the usual “priming” effect, but higher doses were needed for the “facilitatory” effect. Experiments with adrenalectomized-ovariectomized female rats showed that this short latency effect of second estrogen treatment need not be mediated by the adrenals. These results raise the possibility that estrogen acts on the central nervous system in more than one way to induce lordosis.     

The influence of propranolol on the hypotensive action of ketanserin in normotensive rats

In normotensive rats the effect of different doses of propranolol (1.0, 5.0 and 10.0 mg/kg i.p.) and ketanserin (10.0 mg/kg p.o.) on mean blood pressure and heart rate and on cardiovascular response to noradrenaline (0.1, 0.3, 0.5, 0.7 and 1.0 micrograms/kg i.v.) was examined. The drugs were given separately or together. Propranolol slightly reduced the hypotensive effect of ketanserin. On the other hand a decrease in heart rate caused by propranolol was not affected by ketanserin. Our results show that propranolol given with ketanserin did not change the effect of the latter on the cardiovascular system.     

Effect of estrogen on global myocardial ischemia-reperfusion injury in female rats

We investigated the effects of estrogen on global myocardial ischemia-reperfusion injury in rats that were ovariectomized (Ovx), sham-operated, or ovariectomized and then given 17beta-estradiol (E(2)beta) supplementation (Ovx+E(2)beta). Hearts were excised, cannulated, perfused with and then immersed in chilled (4 degrees C) cardioplegia solution for 30 min, and then retrogradely perfused with warm (37 degrees C), oxygenated Krebs-Henseleit bicarbonate buffer for 120 min. The coronary flow rate, first derivative of left ventricular pressure, and nitrite production were all significantly lower in Ovx than in sham-operated or Ovx+E(2)beta hearts. However, coronary flow rates or nitrate production were not consistently different throughout the entire reperfusion period. Ca(2+) accumulated more in Ovx rat hearts than in sham-operated or Ovx+E(2)beta hearts, and mitochondrial respiratory function was lower in Ovx hearts than in hearts from the other two groups. Marked interstitial edema and contraction bands were seen in hematoxylin-eosin-stained sections of Ovx rat hearts but not in hearts from either of the other groups. Hematoxylin-basic fuchsin-picric acid-stained sections revealed fewer viable myocytes in hearts from the Ovx group than from the sham or Ovx+E(2)beta group. Transmission electron microscopy demonstrated more severely damaged mitochondria and ultrastructural damage to myocytes in Ovx rat hearts. Our results indicate that estrogen plays a cardioprotective role in global myocardial ischemia-reperfusion injury in female rats.     

Effect of estrogen pretreatment on the intestinal cytochrome p-450 in female rats

The effect of estrogen hormones on the cytochrome P-45O-linked hydroxylation system of rat small intestine was investigated. Estrogens were found to increase the activity of the intestinal arylhydrocarbon hydroxylase as well as the level of cytochrome P-45O in female rats. There was essentially no difference in the increase of the concentration of cytochrome P-45O due to the duration of pretreatment.     

Role of estrogen in controlling the genital microflora of female rats

Plate counts of viable bacteria recovered by lavage from rat vaginae demonstrated that the number of bacteria associated with the vaginal epithelium varied cyclically and that this pattern was abolished by ovariectomy. After ovariectomy, vaginal bacterial counts remained relatively stable at low levels. The estrogen 17beta-estradiol (1,3,5(10)-estratriene-3,17beta-diol cypionate) administered to ovariectomized rats caused a significant increase in vaginal bacterial counts on day 3 post-treatment. A similar effect was seen in non-ovariectomized rats, but a larger dose of estrogen antagonist may have been present in non-ovariectomized animals. Progesterone (4-pregnene-3,20-dione) given with estradiol diminished the effect of the estrogen on vaginal bacterial counts, but did not abolish it. Progesterone administered without estradiol had no detectable effect on vaginal bacterial counts. These findings suggested that the cyclic variation in bacterial content of rat vaginae could be explained primarily as the effect of the secretory pattern of ovarian estrogen.     

The influence of castration on cell proliferation in the adrenal cortex of female rats

Proliferation kinetics in the zones of the adrenal cortex of female rats after castration are reported. Following ovariectomy a wave of increased cell proliferation was observed in the zona glomerulosa and zona fasciculata after 1 and 2 days respectively. Increased cell proliferation in the zona reticularis was only slight. Cell proliferation returned to the level in control animals at 4 weeks. It is assumed that the regulative process following ovariectomy takes place directly in the adrenal cortex but it is possible that steroid metabolism in the liver is of importance. No relationship between the 3H-TdR labelling index (LI) and the mitotic index (MI) was observed.     

Diabetes abolishes the vascular protective effects of estrogen in female rats

Estrogen is known to exert a protective effect against cardiovascular disease. However, women with diabetes have three times the risk as compared with age-matched non-diabetic women. Our previous study on aortic rings of ovariectomized (OVX) female rats treated with 17-beta-estradiol (E2) demonstrated that the beneficial effect of estrogen is related to the basal release of NO from endothelial cells. In the present study, in order to understand why estrogen protection is abolished in diabetes, we tested vascular responses in OVX, streptozotocin-diabetic female rats and their non-diabetic controls receiving or not E2 replacement. Concentration-response curves to norepinephrine (NE) showed attenuation of the contractile response in E2-treated diabetic, with respect to non-diabetic preparations. This response was further impaired in diabetic, E2-deprived rats. The basal release of NO, as evaluated by concentration-related responses to N(G)-methyl-L-arginine acetate in NE-precontracted aortic rings, was found to be impaired in E2-treated diabetic rats, no further effect being induced by E2 deprivation. The endothelium-dependent relaxation produced by carbachol did not change between groups, whereas the relaxation produced by histamine was enhanced by both diabetes and E2 deprivation. However, E2 treatment counteracted the response to histamine only in preparations from non-diabetic animals. Finally, the relaxation induced by sodium nitroprusside, an endothelium-independent relaxant agent, was comparable between groups. These findings suggest that the lack of protective effects of estrogen in diabetes may be mainly ascribed to the failure of estrogen to reverse the impaired basal release of NO and the abnormal relaxation to histamine, which are observed in the aorta of diabetic rats.     

The influence of long-term estrogen treatments on daily plasma prolactin levels in ovariectomized rats

Prolactin levels were determined in the plasma of female rats from 4 to 54 days after ovariectomy or ovariectomy and treatment with a long acting polymer of estradiol, polyestradiol phosphate (PEP), or Silastic implants of crystalline estradiol-17β. Blood samples were withdrawn from indwelling aortic catheters in the morning (0900–1100) and afternoon (1500–1700). Both methods of estrogen delivery elevated plasma prolactin in the morning and afternoon compared to ovariectomized controls. However, the increases in the afternoon were significantly greater than those in the morning. The difference from ovariectomized controls and the morning-afternoon differences were maintained for 25–26 days in the polyestradiol phosphate-treated group whereas those differences in the group receiving the implants of estradiol were significant for the entire length of the experiment (54 days). In addition, there were periodic fluctuations in the morning and afternoon levels of prolactin in the estradiol implanted animals. It is suggested that the plasma prolactin response to estrogen varies with time of day, time after administration of estrogen and with the method of estrogen delivery.     

Gonadotropin levels in sera and pituitary glands of female rats treated with alloxan

Alloxan monohydrate in saline solution was injected intraperitoneally into young (35 day old) and older (95 day old) female rats at dose levels of 7.5 mg or 15.0 mg/100 g of body wt. In both age groups of rats, only the high dose of alloxan was effective to produce permanent diabetes as judged by the presence of hyperglycemia and glucosuria. The rats were bled by cardiac puncture and autopsied 21 days following the alloxan treatment. In young rats, diabetes resulted in a significant reduction in body weight gain and in ovarian and anterior pituitary weights. Serum and pituitary LH levels of these young diabetics were, respectively, significantly lower and essentially the same, whereas their serum and pituitary FSH levels were, respectively, essentially the same and significantly higher than those of the controls. In the older diabetics, although a significant decrease in body weight gain was observed, the ovarian and pituitary weights as well as the serum and pituitary gonadotropin levels were essentially the same as compared to the controls.