Effects of estradiol on corticosterone secretion in ovariectomized rats

The effects of estradiol benzoate (EB) on steroidogenesis in rat zona fasciculata-reticularis (ZFR) cells were studied. Female rats were ovariectomized (Ovx) for 2 weeks and then injected subcutaneously with oil or EB for 3 days before decapitation. ZFR cells were isolated and incubated with adrenocorticotropin (ACTH) or prolactin (PRL) for 1 h. Corticosterone concentrations in plasma and cell media, and adenosine 3',5'-cyclic monophosphate (cAMP) production in ZFR cells were determined by radioimmunoassay. The effects of EB replacement in vivo on the activities of steroidogenic enzymes in ZFR cells were measured by the amounts of intermediate steroidal products separated by thin-layer chromatography. Replacement of EB in vivo resulted in a dose-dependent increase of plasma PRL and corticosterone in Ovx rats. The basal, ACTH-, and PRL-stimulated release of corticosterone by ZFR cells was greater in EB- than in oil-treated animals. Forskolin-induced production of cAMP was greater in the EB-replaced rats than in oil-treated animals, which correlated with the increase of corticosterone production. The 3-isobutyl-l-methylxanthine (IBMX) plus ACTH-, IBMX plus PRL-, and forskolin plus PRL-stimulated productions of cAMP were higher in EB- than in oil-treated rats. The enzyme activities of postpregnenolone were not affected by EB replacement in Ovx rats. These results suggest that the EB-related increase of corticosterone production in Ovx rats is associated with an increase of cAMP generation and the stimulatory effect of PRL on ZFR cells.     

Effects of estradiol on aldosterone secretion in ovariectomized rats

The effects and action mechanisms of estradiol on aldosterone secretion in female rats were studied. Replacement of estradiol benzoate (EB) increased the levels of plasma estradiol and aldosterone in ovariectomized (Ovx) rats. The aldosterone release from zona glomerulosa (ZG) cells was higher in EB-treated rats than in oil-treated animals. EB treatment potentiated the responses of aldosterone release to adrenocorticotropic hormone (ACTH), forskolin (FSK), and 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP). Administration of EB in vivo did not alter cAMP production in response to ACTH or FSK. Although angiotensin II (Ang II) increased aldosterone secretion by rat ZG cells, the stimulatory effect of Ang II on the release of aldosterone was not altered by EB treatment. The conversions of [3H]-deoxycorticosterone to [3H]-corticosterone and [3H]-corticosterone to [3H]-aldosterone in EB-treated groups were greater than those in the oil-treated group. These results suggest that estradiol increases aldosterone secretion in part through the mechanisms involving the activation of the post-cAMP pathway, 11beta-hydroxylase and aldosterone synthase activity.     

Differential effects of colchicine on central dopaminergic neuronal activity and prolactin secretion in estrogen-primed ovariectomized rats

Colchicine is a potent chemical that disrupts the assembly of microtubulin and affects the integrity of cytoskeleton. It is commonly used to block the axonal transport in neurons. Central administration of colchicine (48 microg/3 microl/rat) two days earlier significantly lowered 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the striatum and nucleus accumbens, both in the morning and in the afternoon. Median eminence DOPAC levels exhibit a diurnal change between morning and afternoon as previously shown. Colchicine treatment lowered and elevated median eminence DOPAC levels in the morning and afternoon, respectively. The estrogen-induced prolactin surge was also blocked. The findings indicate that neuronal inputs are necessary for maintaining basal activities in all dopaminergic neurons, while an inhibitory one predominates in the afternoon for TIDA neurons.     

Characteristics of the effect of estradiol on prolactin secretion by adenohyophyseal cells from intact and ovariectomized rats in primary monolayer cultures]

Estradiol directly stimulated the secretion of prolactin by the adenohypophyseal cells of intact rats in a monolayer culture. Complex interactions between estradiol and some other regulators of the hypophyseal lactotropic function were revealed. It was established that changes in prolactin synthesis and secretion in ovariectomized rats persisted for 3--4 days of adenohypophyseal cell cultivation in vitro.     

Effects of estradiol and estradiol sulfamate on the uterus of ovariectomized or ovariectomized and hypophysectomized rats

Estradiol sulfamate (J995), estradiol-17beta with a substituted sulfamate group in position 3, has much higher systemic estrogenic activity after oral administration than 17beta-estradiol (E2) due to reduced hepatic metabolism of the drug. The lower dose necessary for achievement of adequate systemic estrogenic effects results in a substantial reduction of otherwise commonly observed hepatic side-effects. This makes J995 a strong candidate as an estrogen suitable for oral administration. The present study was performed to examine and compare the effects of J995 and E2 on the uterus after oral or subcutaneous administration to ovariectomized or ovariectomized+hypophysectomized female rats, in particular on the levels of the estrogen receptor (ER) (alpha+beta), ERalpha mRNA and insulin-like growth factor-I (IGF-I) mRNA. The ER levels were determined using a ligand binding assay and the mRNA levels using solution hybridization. The doses of J995 or E2 were chosen to achieve comparable uterotrophic activity. The rats were treated with hormones for 7 days and the treatment was initiated 14 days after surgery. We conclude that there are no major differences in the uterine response to treatment with J995 or E2 with respect to the effects on ER and ERalpha mRNA levels. The IGF-I mRNA level though, is more affected by J995 than by E2 after 7 days of treatment, indicating a prolonged effect of J995.     

Effects of estradiol and estradiol sulfamate on the liver of ovariectomized or ovariectomized and hypophysectomized rats

This study was performed to evaluate and compare the effects of estradiol sulfamate (J995) and estradiol (E2) on the hepatic levels of the estrogen receptor (ER) and its mRNA, in ovariectomized (OVX) and OVX+hypophysectomized (OVXHX) female rats and to study the effects on the liver-derived serum compounds angiotensin I, triglycerides, high-density lipoprotein (HDL) and cholesterol. ER concentrations were determined using ligand-binding assay (LBA) and enzyme immuno assay (EIA), and the mRNA levels using solution hybridization.

The rats were treated orally (p.o.) or subcutaneously (s.c.) for 7 days, with treatments initiated 14 days after surgery.

No differences were found in ER mRNA levels between J995 and E2 treated rats.

The s.c. administered estrogens increased ER levels in OVX rats. Addition of GH+DEX to OVXHX rats restored the ER to levels above those seen in intact rats, whereas simultaneous oral treatment with E2 significantly decreased ER levels again. The s.c. treatment with either J995 or E2 limited the increase caused by addition of GH+DEX.

After oral treatment angiotensin I levels were increased by E2, but not by J995, while triglycerides, HDL and cholesterol levels were decreased by oral E2, J995 showing a similar pattern but was less effective.

In summary, these results on hepatic ER levels and estrogen dependent compounds produced by the liver showed that J995 has a lower impact on the normal liver functions after oral treatment than E2. Thus, J995 is a very promising substance for development of oral estrogen treatment with reduced hepatic side effects.     

Effects of chlorpromazine and estradiol benzoate on prolactin secretion in gonadectomized male and female rats.

The effects of chlorpromazine (CPZ) and estradiol benzoate (EB) on serum prolactin (PRL) levels were studied in gonadectomized male and female rats. In both sexes CPZ (25 mg/kg body weight) produced an elevation of PRL when measured 2 hr after the injection, but the elevated levels were higher in ovariectomized rats than in orchidectomized rats. These results reconfirm a sexual difference in the regulatory mechanism of PRL secretion in response to the dopamine receptor blocker. Pretreatment with 5 microgram EB 48 hr before CPZ injection abolished this sexual difference in serum PRL concentration.     

Effect of estradiol benzoate and clomiphene on tyrosine hydroxylase activity and on luteinizing hormone and prolactin levels in ovariectomized rats

The effects of estradiol benzoate (EB) on tyrosine hydroxylase (TH) activity in the medial basal hypothalamus (MBH) and on plasma levels of luteinizing hormone (LH) and prolactin were studied in long-term ovariectomized rats. Administration of 10 μg EB produced significant elevation of TH activity on Days 1 and 3 following injection. LH levels were significantly lower than controls throughout the three day treatment period, although there was a significant increase from Day 1 to Day 2. TH activity and LH levels were inversely related throughout the experimental period. Clomiphene (15 μg/rat/day), a purported estrogen antagonist, was administered over a period of three days to control and EB-treated rats to determine whether the effect of EB on plasma LH levels was causally related to changes in TH activity. In rats receiving both EB and clomiphene, TH activity was lower and plasma LH was higher than after EB alone. The results support the hypothesis that the feedback effects of estradiol on LH release involve an action on the tuberoinfundibular dopaminergic (TIDA) neurons of the MBH and that clomiphene can oppose the inhibitory effect of estradiol on LH release by directly inhibiting TIDA neuron activity. Furthermore, EB-induced release of prolactin does not appear to involve detectable changes in the activity of TIDA neurons.     

Modulatory effects of the amygdala on oestrogen-induced LH secretion in ovariectomized rats

An increase in LH secretion was induced in ovariectomized oestradiol benzoate-primed rats 5 h after a second injection of oestradiol benzoate. Lesions stereotaxically placed in the cortical and basomedial amygdala of steroid-primed rats abolished this rise. The results provide evidence for a facilitatory action of the amygdala upon LH release and an involvement of this region of the limbic system in oestrogen-feedback mechanisms.     

Influence of season and estradiol on secretion of luteinizing hormone in ovariectomized cows

The hypotheses that secretion of luteinizing hormone (LH) varies with season and that estradiol may modulate the seasonal fluctuation in secretion of LH in cows were investigated. Seven mature cows were ovariectomized approximately 30 days before initiation of the experiment. Three of the ovariectomized cows (OVX-E2) were administered a subcutaneous estradiol implant that provided low circulating levels of 17 beta-estradiol. The remaining 4 cows (OVX) were not implanted. From December 21, 1982, to September 20, 1984, blood samples were collected sequentially (at 10-min intervals for 6 h) at each summer and winter solstice, and each spring and autumn equinox. In addition, from March 17, 1983, to March 17, 1984, sequential samples were collected midway between each solstice and equinox. Concentration of LH was measured in all samples, and concentration of estradiol was measured in pools of samples. An annual cycle in mean serum concentration of LH and amplitude of LH pulses was detected in both groups of cows. The seasonal pattern did not differ in the two treatment groups. Serum concentration of LH and amplitude of LH pulses were highest around the spring equinox, decreased gradually to the autumn equinox, and then increased and peaked again during the following spring equinox. Frequency of LH pulses and concentration of estradiol in serum did not vary with season. Circulating concentrations of LH and amplitude of pulses tended to be higher in OVX-E2 than OVX cows throughout the experimental period. Frequency of pulses of LH was lower in OVX-E2 than OVX cows throughout the experiment. Concentrations of estradiol were higher in the implanted cows.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibitory effects of adrenocorticotrophin or corticosterone on progesterone secretion during mid-pregnancy in rats

Conceptus number was reduced to one on Day 7 of pregnancy in rats by aspirating all but a single conceptus (Group E) or left at greater than or equal to 8 conceptuses (Group C). In Group E rats, serum progesterone concentrations remained low from Day 12 until autopsy at Day 21. Hypophysectomy on Day 12 significantly increased serum progesterone values after Day 17 of pregnancy, and these increases were blocked by treatment with ACTH (10 U/day, i.p., Days 12-17). Adrenalectomy on Day 12 also induced slight, but statistically significant, increases in serum progesterone concentration after Day 17, and these were overcome by implantation of a 10 mg capsule of corticosterone. In Group C rats, hypophysectomy or adrenalectomy on Day 12 did not change serum progesterone concentrations, but 40 U ACTH/day inhibited progesterone secretion. We conclude from these results that the pituitary-adrenal system exerts inhibitory effects on progesterone secretion during mid-pregnancy in rats.     

Direct effects of prolactin on corticosterone release by zona fasciculata-reticularis cells from male rats

The role of prolactin (PRL) in the male is not fully defined. The aim of this study was to investigate the function and mechanism of PRL on the production of corticosterone by zona fasciculata-reticularis (ZFR) cells in vitro. The ZFR cells were obtained from male rats under normal, hyperprolactinemic, or hypoprolactinemic situation. PRL stimulated the corticosterone release in a dose-dependent pattern in the ZFR cells from normal male rats. The cellular adenosine 3'-5'-cyclic monophosphate (cAMP) concentration positively correlated with PRL concentration in the presence of forskolin or 3-isobutyl-1-methylxanthine (IBMX). PRL enhanced the stimulatory effects of cAMP mimetic reagents, i.e., forskolin, 8-bromo-adenosine 3',5'-cyclic monophosphate (8-Br-cAMP), and IBMX on the release of corticosterone. The adenylate cyclase inhibitor (SQ22536) inhibited the corticosterone release in spite of presence of PRL. Nifedipine (L-type calcium channel blocker) did not inhibit corticosterone release. The hyperprolactinemic condition was actualized by transplantation of donor rat anterior pituitary glands (APs) under kidney capsule. By comparison with the cerebral cortex (CX)-grafted group, AP-graft resulted in an increased release of corticosterone, 3beta-hydroxysteriod dehydrogenase (HSD) activity and cAMP production by ZFR cells. Acute hypoprolactinemic status was induced by bromocriptine for 2 days. The results showed the productions of corticosterone were lower in hypoprolactinemic group than in control group, which were persistent along with different ACTH concentrations. These results suggest that PRL increase the release of corticosterone by ZFR cells via cAMP cascades and 3beta-HSD activity.     

Novel 8 alpha-ergolines with inhibitory and stimulatory effects on prolactin secretion in rats

Four derivatives of the ergot dopamine (DA) agonist lisuride (LIS), namely 6-n-propyl-lisuride (6-n-propyl-LIS), transdihydrolisuride (TDHL), 6-n-propyl-transdi-hydrolisuride (6-n-propyl-TDHL) and 2-bromolisuride (2-Br-LIS) were investigated in female rats with regard to their influence on hyperprolactinaemia induced by pretreatment with reserpine (2 mg/kg i.p., 24 h) at various intervals following their subcutaneous or oral administration (0.05 mg/kg). Two hours after administration, LIS, 6-n-propyl-LIS, and 6-n-propyl-TDHL caused a statistically significant inhibition of reserpine-induced hyperprolactinaemia of about the same extent. Eight hours after administration 6-n-propyl-LIS and 6-n-propyl-TDHL were as active as after 2 h in inhibiting prolactin (PRL) secretion whereas LIS was almost ineffective in this respect. TDHL caused a statistically significant inhibition of PRL secretion at 2 and 8 h after oral administration; this effect was less pronounced after s.c. administration. In contrast to the aforementioned derivatives 2-Br-LIS further increased the reserpine-induced hyperprolactinaemia. In normal male rats pretreatment with 2-Br-LIS (0.025-6.25 mg/kg s.c., 2 h) dose-dependently stimulated PRL secretion. The present data support the assumption of the longlasting DA agonistic action of 6-n-propyl-LIS and 6-n-propyl-TDHL and of the antidopaminergic properties of 2-Br-LIS recently derived from behavioural studies.     

Transgenerational effects of social stress on social behavior,corticosterone, oxytocin,and prolactin in rats

Social stressors such as depressed maternal care and family conflict are robust challenges which can have long-term physiological and behavioral effects on offspring and future generations. The current study investigates the transgenerational effects of an ethologically relevant chronic social stress on the behavior and endocrinology of juvenile and adult rats. Exposure to chronic social stress during lactation impairs maternal care in F0 lactating dams and the maternal care of the F1 offspring of those stressed F0 dams. The overall hypothesis was that the male and female F2 offspring of stressed F1 dams would display decreased social behavior as both juveniles and adults and that these behavioral effects would be accompanied by changes in plasma corticosterone, prolactin, and oxytocin. Both the female and male F2 offspring of dams exposed to chronic social stress displayed decreased social behavior as juveniles and adults, and these behavioral effects were accompanied by decreases in basal concentrations of corticosterone in both sexes, as well as elevated juvenile oxytocin and decreased adult prolactin in the female offspring. The data support the conclusion that social stress has transgenerational effects on the social behavior of the female and male offspring which are mediated by changes in the hypothalamic–pituitary–adrenal axis and hypothalamic–pituitary–gonadal axis. Social stress models are valuable resources in the study of the transgenerational effects of stress on the behavioral endocrinology of disorders such as depression, anxiety, autism, and other disorders involving disrupted social behavior.     

Effects of fasting on aldosterone secretion in ovariectomized rats

The present study was designed to assess the effect of fasting on aldosterone secretion in ovariectomized (Ovx) rats. Ovx rats were divided into fed (allowed access to food ad libitum) and fasted (deprived of food for 24 hours) groups. The trunk blood of fed and fasted rats was collected after decapitation. In the in vitro study, adrenal zona glomerulosa (ZG) cells from fed or fasted rats were incubated with angiotensin II (Ang II, 10(-6) M), adrenocorticotropic hormone (ACTH, 10(-9) M), or forskolin (an activator of adenylyl cyclase, 10(-6) M) at 37 degrees C for 30 min. The levels of aldosterone in medium and plasma extracts were measured by radioimmunoassay. Results showed that the levels of plasma aldosterone in fasted rats were lower than those in fed rats. There were no significant differences in basal and Ang II-stimulated aldosterone secretion between fed and fasted groups. The increment of aldosterone induced by ACTH in fasted group was significantly less than that in fed group. Administration of forskolin led to a significant increase in aldosterone secretion in both fed and fasted groups. Fasted group had a decreased aldosterone secretion in response to forskolin as compared with fed group. In summary, these results suggest that fasting decreases aldosterone secretion in Ovx rats through a mechanism in part involving a reduction of aldosterone production in response to ACTH, a decreased activity of adenylyl cyclase, and/or an inhibition of post-cAMP pathway in ZG cells.     

Influence of corticosterone acetate on the spleen in intact and ovariectomized rats.

Increasing evidence of the interaction of glucocorticoids and ovarian steroids prompted the current study. Effects of exogenously administered corticosterone acetate (3.5 mg/100 g b.w/day for one week) were examined on splenic nucleic acids, protein, lactate, and on lactate dehydrogenase (LDH) specific activity and its isozymes in ovariectomized and ovary-intact Wistar rats (65-75 days old). Ovariectomy resulted in no significant change in the parameters studied except DNA which increased significantly. The administration of corticosterone to these rats did not produce any remarkable change in the ovariectomy caused increase in splenic DNA content. Nevertheless, it decreased the ratio of heart type subunits (H)/muscle type subunits (M) [H/M] of LDH isozymes. In the case of ovary-intact rats, corticosterone produced an increase in the concentration of splenic lactate but a decrease in the H/M ratio. Exogenously administered corticosterone exerts selective synergistic interaction with ovarian hormones on splenic lactate. The specific activity of LDH and the concentrations of RNA and protein remained unchanged during the interaction between ovarian hormones and corticosterone.