OVEX Rats Research Articles

Estrogen Replacement Improves Mesenteric Arterial Relaxation in UC Davis Pre‐diabetic Rats: Possible Involvement of Estrogen Receptor Beta

The risk of cardiovascular diseases (CVD) is lower in premenopausal women compared to men, and this lower risk is related to the presumptive cardioprotective effects of female sex hormones, estrogen in particular. However, premenopausal women may lose this protection with the onset of menopause and/or when they become diabetic. Little is known about the vascular function in presence or absence of estrogen at the early stage of diabetes.The objective of this study was to investigate the effects of 17β‐estradiol (E2) replacement on mesenteric arterial (MA) function in ovariectomized (ovex) UC Davis type 2 diabetes mellitus (UCD‐T2DM) rats at the pre‐diabetic stage. MA were obtained from four groups of ovex rats implanted with a subcutaneous pellet for 45 days: (1) Control (Ctrl), ovex + placebo, (2) Ctrl, ovex + E2 (1.5mg/pellet), (3) pre‐diabetic, ovex + placebo, (4) pre‐diabetic, ovex + E2. Endothelium‐dependent vasodilation (EDV) to acetylcholine (ACh, 10−8 to 10−5 M) in MA were measured before and after indomethacin (Indo, 10μM), a cyclooxygenase (COX) inhibitor; followed by addition of L‐NAME (200μM), a nitric oxide synthase (NOS) inhibitor. The MA expression of estrogen receptors (ERs) and plasma E2 concentration were determined by Western blotting and ELISA assay, respectively.E2 treatment significantly increased plasma estradiol concentration in both Ctrl and Prediabetic groups. Analysis of ERs showed a higher expression of ER‐beta only in E2‐treated prediabetic group. ACh responses were similar in Ctrl groups, regardless of E2 replacement. ACh induced relaxation was, however, markedly reduced in MA of placebo treated pre‐diabetic group compared with other groups. Treatment of pre‐diabetic with E2 enhanced relaxation to the same level as those from Ctrl rats. Blocking of both COX and NOS completely abolished the relaxation responses to ACh in pre‐diabetic groups, regardless of E2 replacement, indicating no contribution of EDHF‐type relaxation in these groups. However, the added effect of L‐NAME, in presence of Indo, in blocking ACh‐mediated vasodilation was much more prominent in E2‐treated prediabetic group when compared with placebo treated group, indicating an enhanced role of NO. On the other hand, both NO and EDHF remained important for EDV in Ctrl groups. Addition of L‐NAME, however, caused a much smaller reduction of EDV in E2 treated than in placebo treated arteries, suggesting EDHF is the predominant mediator of mesenteric vasorelaxation in this groups.Here, we show that EDV is impaired at pre‐diabetic stage, may be due to loss of EDHF. E2 treatment restores EDV in MA of pre‐diabetic group, possibly via elevated contribution of NO‐mediated relaxation by increased E2 signaling (via ER beta) in this group. The role of ER alpha remains to be investigated.Support or Funding InformationSupported by NHLBI.

Anxiogenic CO2 stimulus elicits exacerbated hot flash-like responses in a rat menopause model and hot flashes in postmenopausal women.

As longitudinal studies determined that anxiety is a strong risk factor for hot flashes, we hypothesized that an anxiogenic stimulus that signals air hunger (hypercapnic, normoxic gas) would trigger an exacerbated hot flash-associated increase in tail skin temperature (TST) in a rat ovariectomy (OVEX) model of surgical menopause and hot flashes in symptomatic postmenopausal women. We also assessed TST responses in OVEX serotonin transporter (SERT) rats that models a common polymorphism that is associated with increased climacteric symptoms in postmenopausal women and increases in anxiety traits. OVEX and sham-OVEX rats (initial experiment) and wildtype and SERT OVEX rats (subsequent experiment) were exposed to a 5-minute infusion of 20% carbon dioxide (CO2) normoxic gas while measuring TST. Postmenopausal women were given brief 20% and 35% CO2 challenges, and hot flashes were self-reported and objectively verified. Compared to controls, OVEX rats had exacerbated increases in TST, and SERT OVEX rats had prolonged TST increases following CO2. Most women reported mild/moderate hot flashes after CO2 challenges, and the hot flash severity to CO2 was positively correlated with daily hot flash frequency. The studies demonstrate that this anxiogenic stimulus is capable of inducing cutaneous vasomotor responses in OVEX rats, and eliciting hot flashes in postmenopausal women. In rats, the severity of the response was mediated by loss of ovarian function and increased anxiety traits (SERT), and, in women, by daily hot flash frequency. These findings may provide insights into anxiety-related triggers and genetic risk factors for hot flashes in thermoneutral environments.

The determination of apoptosis rates on articular cartilages of ovariectomized rats with and without alendronate treatment.

Osteoporosis (OP) is a major health problem characterized by compromised bone strength. Osteoarthritis (OA) is a joint disease that progresses slowly and is characterized by breakdown of the cartilage matrix. Alendronate (ALN), a nitrogen-containing bisphosphonate (BIS), inhibits bone loss and increases bone mineralization, and has been used clinically for the treatment of OP. It is still controversial whether BIS is effective in inhibiting the progression of OA. Chondrocyte apoptosis has been described in both human and experimentally induced OA models. In our study we aimed to detect whether ALN could protect articular cartilage from degeneration and reduce apoptosis rates in experimentally OA induced rats. For this rats were ovariectomized (ovex), nine weeks after operation rats were injected 30 µg/kg/week ALN subcutaneously for six weeks. After six weeks articular cartilages were obtained. We did Safranin O staining and Mankin and Pritzker scorings to evaluate degeneration and investigated the expressions of p53, cleaved caspase 3, Poly ADP-ribose (PAR), Poly ADP-ribose polymerase 1 (PARP 1), and applied TUNEL technique to determine apoptotis rates. We found a significant decrease in glycosaminoglycan (GAG) amount and increased apoptosis which indicates damage on articular cartilages of ovex rats. GAG amount was higher and apoptosis rate was lower on articular cartilages of ALN treated ovex rats compared to the ovex group. In contrary to studies showing that early ALN treatment has a protective effect, our study shows late ALN treatment has a chondroprotective effect on articular cartilage since we treated rats nine weeks after ovariectomy.

Voluntary running exercise attenuates the progression of endothelial dysfunction and arterial calcification in ovariectomized rats

Loss of oestrogen synthesis capacity after menopause contributes to increases in arterial stiffness and calcification. Exercise training improves arterial stiffness and calcification. However, the mechanism of exercise training-induced improvement of arterial stiffness and calcification remains unclear. We examined the mechanism by using aortas of sham-operated rats (sham control; SC), ovariectomized rats (OVX control; OC), OVX plus treatment with vitamin D(3) plus nicotine (VDN) rats (OV sedentary; OVSe), which is an animal model of endothelial dysfunction and arterial calcification, and voluntary running wheel exercise for 8 weeks plus OVX plus VDN rats (OV exercise; OVEx). The arterial tissue calcium and endothelin-1 (ET-1: a vasoconstrictor peptide and a potent regulator of arterial calcification) levels were significantly higher in OVSe rats compared with the SC and OC rats, whereas these levels in the OVEx rats were significantly lower than in the OVSe rats. Additionally, arterial expression of endothelial nitric oxide synthase (eNOS), which is an enzyme that produces nitric oxide (NO: a vasodilator substance), was reduced in OVSe rats. However, exercise training prevented the decrease in eNOS expression. Moreover, there was a significant positive correlation between arterial calcium level and arterial ET-1 level. These findings suggest that exercise training-induced improvement of ET-1 and NO prevents the impairment of endothelial function after menopause in females, and this improvement may result in less arterial calcification.

Endothelial‐dependent and –independent vasodilation in cerebral resistance arteries: Effects of age and estrogen Status

At menopause, women undergo an increase in risk for cardiovascular disease. Estrogen is known to play a role in modulating vascular function and providing protective cardiovascular effects. However, it is not known whether the protective cardiovascular effects of estrogen change with age. Therefore, the purpose of this study was to determine effects of age and estrogen status on endothelial-dependent and –independent vasodilation in cerebral resistance arteries. Posterior communicating arteries (PCoA) were isolated from young (6 mo), middle aged (14 mo), and old (24 mo) in control (CON) and ovariectomized (OVEX) female Fischer-344 rats, and flow-, acetylcholine (ACh-), and DEA-NONOate–induced vasodilation were assessed. Flow-induced vasodilation (FID) of the PCoA was preserved with age in intact female rats (6 mo: 73.9 ± 5.4 % vs. 24 mo: 82.4 ± 7.1%), but OVEX rats exhibited a lower FID in contrast to intact female rats (Ovex: 68.0 ± 4.1 % vs. CON: 79.8 ± 3.6%). Endothelium-dependent dilation to ACh declined with age (6 mo: 51.3 ± 4.5%; 14 mo: 40.0 ± 5.9%; 24 mo: 33.2 ± 4.9%); however, ACh-induced dilation increased in OVEX young rats (Ovex: 57.4 ± 6.9% vs. CON: 45.2 ± 5.9%). No age effect was present in DEA-NONOate treated vessels. These data suggest both age and circulating ovarian hormones are determinants of vascular reactivity in cerebral resistance arteries and influence the risk for cerebral vascular disease. Funded by NIH grant HL077224.

Modulation of hypoglycemia‐induced increases in plasma epinephrine by estrogen in the female rat

Clinical studies have demonstrated that estrogen replacement therapy suppresses stress-induced increases in plasma catecholamines. The present study determined whether normal circulating levels of estrogen can modulate hypoglycemia-induced increases in plasma epinephrine (EPI). In anesthetized female rats, insulin-induced hypoglycemia (0.25 U/kg) increased plasma EPI concentration to a significantly greater extent in 14-day ovariectomized (OVEX) rats compared to that in sham-operated controls. In 17beta-estradiol (E2)-replaced OVEX rats, the hypoglycemia-induced rise in plasma EPI was reduced significantly when compared to that in vehicle-replaced OVEX rats. OVEX and E2 replacement had no effect on tyrosine hydroxylase or phenylethanolamine N-methyltransferase mRNA levels in the adrenal medulla. In isolated adrenal medullary chromaffin cells, agonist-induced increases in intracellular Ca2+ were unaffected by 48-hr exposure to 10 nM E2. In contrast, acute (3-min) exposure to micromolar concentrations of E2 dose-dependently and reversibly inhibited agonist-induced Ca2+ transients. In addition, in OVEX rats, a constant infusion of E2 significantly reduced the insulin-induced increase in plasma EPI concentration compared to that in vehicle-infused controls. These data demonstrate that physiologic levels of circulating E2 can modulate hypoglycemia-induced increases in plasma EPI. This effect seems independent of steroid influence on adrenal medullary secretion or biosynthesis. In contrast, acute exposure to high levels of E2 can also suppress hypoglycemia-induced increases in plasma epinephrine, due at least in part to inhibition of stimulus-secretion coupling.

Estrogen promotes microvascular pathology in female stroke-prone spontaneously hypertensive rats (SHRSP)

Estrogen produces both beneficial and adverse effects on cardiovascular health via mechanisms that remain unclear. Female SHRSP maintainedon a high-salt intake rapidly develop stroke and malignant nephrosclerosis. To determine whether estrogen contributes to stroke-related mortality in this model, we examined the effect of ovariectomy with or without estradiol benzoate (E2) therapy and antiestrogen treatment with tamoxifen. SHRSP were ovariectomized (Ovex) or sham operated (Sham) at 4 weeks of age and then dosed chronically with E2 at 10 μg/Kg 3 times a week or vehicle (VEH) starting at 5 weeks of age. All SHRSP received 1% NaCl drinking solution starting at 8 weeks of age. Ovex rats lived significantly (P<0.01) longer (15.1±0.3 weeks, n=4) than Sham (13.6±0.2 weeks, n=6) or Ovex & E2 (12.4±0.2 weeks, n=7). In a second survival study, six saline-drinking female SHRSP with intact ovaries received 2.3 mg/Kg of tamoxifen 3 times a week and six non-ovariectomized littermates received VEH. Tamoxifen treatment delayed the onset of stroke-related mortality by at least two weeks (P<0.01) but did not prevent the development of severe hypertension. Ovex (n=13), Sham (n=14), and Ovex & E2 (n=9) SHRSP that were sacrificed at 11.5 weeks of age were also studied so that renal microvascular injury could be assessed in groups that were matched for age. Systolic blood pressure (SBP) prior to death was lower in Ovex compared with Sham and Ovex & E2 but did not differ between Sham and Ovex & E2 (Table). Ovex & E2had elevated blood urea nitrogen (BUN), proteinuria and renal lesions of thrombotic microangiopathy (TMA) compared with either Sham or Ovex. Ovex & E2 developed worse pathology than Sham, perhaps due to the absence of vascular protective factors from the ovary. Consistent with the ability of Ovex to diminish endogenous estrogen levels, uterine dry weight (mg) was significantly less in Ovex (8±1) compared to Sham (76±4) and Ovex & E2 (59±3). The results of these studies suggest that estrogen plays a role in promoting stroke and renal microvascular injury in saline-drinking female SHRSP. Values are mean ± SEM; P<0.01 vs Ovex; #P<0.01 vs Sham Values are mean ± SEM; P<0.01 vs Ovex; #P<0.01 vs Sham

Effects of Various Doses of 17.BETA.-estradiol on the Progression of Mammary Carcinomas Induced by Single and Multiple Administration of 7,12-Dimethylbenz[a]anthracene in Female Rats.

The objective of this investigation was to elucidate the role of sex hormones in the progression and subsequent hormone dependency of mammary carcinomas induced by single or multiple administration of 7, 12-dimethylbenz[a]anthracene (DMBA). Ten milligrams of DMBA were administrated orally to female Sprague-Dawley (SD) rats once at the age of 42 days (Group A) and three times at the ages of 28, 42 and 56 days (Group B). All 70-day-old rats in Groups A and B were divided into 4 groups (I, II, III and IV), respectively. Rats in Groups I of A and B were intact controls. Rats in Groups II of A and B were ovariectomized (OVEX) at the age of 70 days. Rats in Group II of Group A and in Groups III of Groups A and B were divided into 4 subgroups (Group II-1, II-2, II-3 and II-4) and 3 subgroups (Group III-1, III-2 and III-3), respectively. Rats in Groups II-2 of A and III-1 of A and B, rats in Groups II-3 of A and III-2 of A and B and rats in Groups II-4 of A and III-3 of A and B were given injections of 0.01, 0.1 and 1 mg 17β-estradiol (E2), respectively. Rats in Groups IV of A and B were given injections of 4 mg progesterone (P). Injections of E2 or P were given 3 times a week between the ages of 70 and 217 days in Group A and the ages of 70 and 105 days in Group B. In Group A, there was no difference of incidence of mammary carcinomas among Groups I, II-2, II-4, III-1 and IV but the incidence of mammary carcinomas in Groups II-1, II-3, III-2 and III-3 was extremely low, compared with that in Group I. In Group B, a large number of mammary carcinomas developed and although there was no difference in the incidence of mammary carcinomas among Groups I, II, III and IV, the number of mammary carcinomas per rat decreased in Groups II, III-2 and III-3, compared with Group I. These findings indicate that the progression of mammary carcinomas induced by a single or multiple administration of DMBA was suppressed in ovariectomized rats and in rats with injections of high doses of E2. DMBA-induced mammary carcinomas in Group B were transplanted into OVEX rats (R-1), OVEX rats with injections of 0.01 mg E2 (R-2) and OVEX rats with injections of 1 mg E2 (R-3). According to tumorigenesis in those rats with various hormonal treatments (R-1, 2, 3), mammary carcinomas were classified into one of the four categories (Type A, B, C and D). Type A tumor: tumor developed greatly in R-2 but slightly or not in R-1 and R-3. Type B tumor: tumors developed greatly in R-1 but slightly or not in R-2 and R-3. Type C tumor: tumors developed greatly in R-3 but slightly or not in R-1 and R-2. Type D tumor: tumors developed greatly in R-1, R-2 and R-3. In Group B, rates of type A, B, C, D tumor were 43.2, 13.5, 24.3 and 18.9% in Group I, 26.3, 10.5, 21.1 and 42.1% in Group II, 40.0, 5.0, 45.0 and 10.0% in Group III-1, 38.5, 15.4, 30.8 and 15.4% in Group III-2, 28.6, 0, 71.4 and 0% in Group III-3 and 44.4, 33.3, 11.1 and 11.1 in Group IV, respectively. These results suggested that the hormonal status of the development process may be one of factors which affects the characteristics of hormone dependency and the multiple administration of DMBA may induce large numbers of carcinoma cells with varying dependency on hormones and carcinoma cells may be selected in hormonal conditions during progression.

Stimulatory effects of retinoic acid on tumor growth and serum insulin-like growth factor-1 in rats bearing estrogen-responsive pituitary tumor MtT/Se.

MtT/Se is one of 4 cell lines derived from an estrogen‐dependent pituitary tumor, MtT/F84. The main difference between these tumor types is that MtT/F84 secretes both growth hormone (GH) and prolactin (PRL) whereas MtT/Se secretes only GH. MtT/Se grew slowly in ovariectomized (ovex) rats, but tumor growth was much faster in estrogen‐treated ovex rats. Effects of dietary retinoic acid (RA) on tumor growth, serum GH and insulin‐like growth factor‐1 (IGF‐1) levels were examined in ovex rats. Latency of tumor growth was shortened, and tumor take and weight were promoted by all‐trans RA both in the presence and absence of exogenous estrogen. Serum GH and IGF‐1 levels became increased in tumor‐hearing rats whereas PRL levels remained unchanged. Serum IGF‐1 levels exhibited a good correlation with tumor weights (r=0.84). Our results suggest a close relationship between increase of tumor weight and stimulation of serum IGF‐1 level by RA in tumor‐bearing rats.

The Preovulatory Prolactin Surge Is Prolonged by a Progesterone-Dependent Dopaminergic Mechanism*

The preovulatory PRL surge consists of a sharp peak, a prolonged plateau, and a termination phase. This study examined the role of progesterone in maintaining elevated PRL release during the plateau phase and its effect on dopaminergic (DA) neuronal activity. Immature rats were injected with PMSG on day 28, and blood was collected during the periovulatory period. Plasma estradiol levels were elevated before and during the PRL peak and declined during the plateau. Plasma progesterone levels were low before and during the peak, rose 4- to 5-fold during the plateau, and decreased to basal levels at the termination phase. In a second experiment rats were subjected to acute ovariectomy (OVEX) or sham surgery (SHAM) just before the onset of the PRL surge. Some OVEX rats were either immediately implanted with an estradiol-containing capsule or given three injections of progesterone during the time of the plateau phase. Blood PRL levels in SHAM rats showed the typical peak, plateau, and termination phases. The PRL peak was evident, but the plateau was missing in OVEX rats with or without estradiol treatment. Replacement with progesterone restored the plateau. In a third experiment, the stalk-median eminence, posterior pituitary, and striatum were removed during the time of the midplateau phase. Tyrosine hydroxylase activity was determined in tissue homogenates by a coupled hydroxylation-decarboxylation assay. Tyrosine hydroxylase activity in the stalk-median eminence of SHAM and progesterone-treated OVEX rats was similar, but was significantly lower than that in OVEX rats with or without estradiol. Tyrosine hydroxylase activity in the posterior pituitary and striatum was unchanged. To assess the functional DA input to the anterior pituitary, haloperidol, a DA antagonist, was injected during the midplateau phase. It induced a 12- to 17-fold rise in plasma PRL in both untreated and estradiol-treated OVEX rats, but failed to increase PRL above the plateau levels in SHAM and progesterone-treated OVEX rats. We conclude that the plateau phase of the preovulatory PRL surge is dependent on the concomitant rise in progesterone. Progesterone probably acts by reducing the DA neuronal activity in the SME, resulting in an absence of functional DA input to anterior pituitary lactotrophs.

Antiestrogen(4-hydroxytamoxifen)-charged estrogen receptor binding to nuclei from normal and neoplastic rat mammary tissues is not affected by host hormonal status

Interaction of [ 3H]4-hydroxytamoxifen-charged estrogen receptor ([ 3H]AER) with nuclei was compared to that of [ 3H]17β-estradiol-charged estrogen receptor ([ 3H]ER) in vitro. Specificity of [ 3H]AER binding was demonstrated since more than 90% of [ 3H]AER binding was displaced by ten-fold excess estradiol-charged ER. For R3230AC tumors, the number of [ 3H]AER binding sites was approximately 40% lower than the number of [ 3H]ER binding sites. There were no differences in affinity of binding of these receptor complexes ( K d range 0.7–1.6 nM). In contrast to a reduction of [ 3H]ER binding after ovariectomy, no difference in the number of [ 3H]AER binding sites was seen among tumors from intact, ovex, or estrogen-treated ovex rats. These results suggest that [ 3H]AER bind to 60% of the sites that bind [ 3H]er, and that neither tissue type nor host ovarian status affects the number of nuclear [ 3H]AER binding sites.

Chronic inhibition of hypothalamic-pituitary-ovarian axis and body weight gain by brain-directed delivery of estradiol-17 beta in female rats.

The effect of preferential delivery of estradiol (E2) into the brain on both the hypothalamic-pituitary-ovarian axis and weight gain was studied in female rats. When E2 was coupled to a lipoidal dihydropyridine-pyridinium carrier, the resulting carrier E2 complex (CE), upon a single intravenous administration to cycling female rats, caused a dose-dependent inhibition of ovulation which lasted 3 times longer than with uncoupled E2. The dose of CE that delayed ovulation for 4 days was one twentieth the amount of E2 needed to produce the same effect. Studies in ovariectomized (OVEX) rats indicated that the prolonged ovulation-blocking action of CE appeared to be related to a sustained storage and release of E2 in the brain, which in turn suppressed the release of hypothalamic luteinizing hormone-releasing hormone (LHRH) and pituitary luteinizing hormone (LH). Upon single intravenous administration in pubertal female rats, CE caused a dose-dependent reduction of body weight gain for a minimum period of 28 days. The inhibitory action of CE on body weight gain was more potent and longer lasting than that of E2 in pubertal rats. When administered in OVEX rats, CE produced a loss of body weight that lasted significantly longer than that produced by uncoupled E2 in these rats. These results suggest that the biological action of E2 can be potentiated by this novel chemical delivery system.

Prolactin secretion in posterior pituitary lobectomized rats: differential effects of 5-hydroxytryptophan and ether

The objective of this study was to determine whether the posterior pituitary mediates the prolactin (PRL) releasing activities of serotonin and ether. Ovariectomized (OVEX) rats were subjected to posterior pituitary lobectomy (LOBEX) or sham surgery (SHAM). Either 1 or 12 days after surgery, rats were injected i.v. with 20 mg/kg b. wt. of 5-hydroxytryptophan (5-HTP), which is a precursor of serotonin. A second group of rats was exposed to ether vapors for 10 min. Blood was collected from a jugular cannula before and after the treatments and analyzed for PRL. On either 1 or 12 days after surgery, injection of 5-HTP increased plasma PRL levels 5–10 fold in both LOBEX and SHAM rats. This was followed by a decline to preinjection levels within 60–90 min. LOBEX and SHAM male rats which were injected i.p. with 50 mg/kg b. wt. of 5-HTP, also showed marked and similar elevations of plasma PRL levels 12 days after surgery. Exposure of OVEX rats to ether elicited a 2–3 fold rise in plasma PRL levels only on day 1, but not on day 12, after LOBEX. The ether-induced rise in PRL was similar in SHAM rats tested on both days. These results indicate that the 5-HTP-induced rise in plasma PRL levels is independent of the posterior pituitary, regardless of the sex, the route of drug administration or the length of time after surgery. In contrast, the PRL response to ether stress is diminished within 12 days after LOBEX. The evidence that the PRL responses to 5-HTP and to ether might be mediated via different neuronal mechanisms is discussed.

The physiological significance of the hippocampus on the inhibitory effects of corticosterone upon the estradiol-induced LH and FSH surges in rats

The effects of corticosterone (CS) on the gonadotropin surge induced by estradiol-benzoate (E2) were studied in adrenalectomized and ovariectomized (ADRX-OVEX) rats. The results are as follows. In ADRX-OVEX rats implanted with E2-tablets in the bilateral axillae, LH and FSH surges occurred 4 days after the implantation of E2, peaking at 17:00 h. The levels of these surges were markedly higher than those in OVEX rats similarly treated but were attenuated significantly by the subcutaneous injection of CS (25 micrograms in sesame oil) given at 12:00 h. The CS implantation (0.5 micrograms in 2 microliters sesame oil) into the dorsal hippocampus at 15:00 h significantly inhibited the levels of LH and FSH surges in ADRX-OVEX rats with E2-tablets. The effect of the CS implant in the lateral septal nucleus was also inhibitory but not statistically significant. The CS administration in the ventral part of the midbrain tegmentum did not elicit any change in the surge of LH and FSH. In animals with the dorsal fornix-section at the post-anterior-commissural level, surges of LH and FSH also occurred in the afternoon of the 4th day after the E2-tablets implantation, but the levels of LH and FSH were not significantly altered by an intravenous injection of CS (5 micrograms in saline) at 15:30 h. It was suggested the CS circulating in the blood would induce a rise of hippocampal activity which would exert a suppressive influence on the gonadotropin release.

Ovarian steroid effects on light-induced retinal photoreceptor damage

Light-induced degeneration in intact and ovariectomized (OVEX) albino rats was compared to that in OVEX rats receiving graded dosages of estradiol benzoate (EB) and progesterone (2·5 mg/day). Retinal damage was not as severe in OVEX rats as in intact or sham-operated animals. Treatment with 0·05 μg EB reversed the protection afforded by OVEX, while treatment with 100 μg EB significantly reduced the damage, even more than by OVEX alone. Progesterone was ineffective in modifying photoreceptor damage. Results are discussed in relation to whether the estrogen effect on the retina influences specific steroid receptor sites or an enzyme system in the photoreceptor cells.