Acute effects of unilateral sectioning the superior ovarian nerve of rats with unilateral ovariectomy on ovarian hormones (progesterone,testosterone and estradiol) levels vary during the estrous cycle

The present study analyzed the participation of the left and right superior ovarian nerves (SON) in regulating progesterone, testosterone, and estradiol serum levels in unilaterally ovariectomized rats on each day of the estrous cycle. For this purpose, ovarian hormone concentrations in serum were measured in animals with either sham-surgery, unilateral ovariectomy (ULO), unilateral sectioning of the SON, or sectioning of the SON innervation of the in situ ovary in rats with ULO.     

Unilateral sectioning of the superior ovarian nerve of rats with polycystic ovarian syndrome restores ovulation in the innervated ovary

The present study tested the hypothesis that if polycystic ovary syndrome (PCOS) results from activating the noradrenergic outflow to the ovary, unilaterally sectioning the superior ovarian nerve (SON) will result in ovulation by the denervated ovary, and the restoration of progesterone (P4), testosterone (T) and estradiol (E2) normal serum level. A single 2 mg dose of estradiol valerate (EV) to adult rats results in the development of a syndrome similar to the human PCOS. Ten-day old rats were injected with EV or vehicle solution (Vh) and were submitted to sham surgery, unilateral or bilateral sectioning of the SON at 24-days of age. The animals were sacrificed at 90 to 92 days of age, when they presented vaginal estrus preceded by a pro-estrus smear. In EV-treated animals, unilateral sectioning of the SON restored ovulation by the innervated ovary and unilateral or bilateral sectioning of the SON normalized testosterone and estradiol levels. These results suggest that aside from an increase in ovarian noradrenergic tone in the ovaries, in the pathogenesis of the PCOS participate other neural influences arriving to the ovaries via the SON, regulating spontaneous ovulation. Changes in P4, T and E2 serum levels induced by EV treatment seem to be controlled by neural signals arising from the abdominal wall and other signals arriving to the ovaries through the SON, and presents asymmetry.     

Ipsilateral vagotomy to unilaterally ovariectomized pre-pubertal rats modifies compensatory ovarian responses

The present study evaluates the participation of the vagus nerve in pre-pubertal rats with unilateral ovariectomy on puberty onset, and on progesterone, testosterone and estradiol serum levels, and the compensatory responses of the ovary. Unilateral vagotomy did not modify the onset of puberty in unilaterally ovariectomized rats. Ovulation rates of animals with the left vagus nerve sectioned and the left ovary in-situ was lower than in rats with only unilateral ovariectomy. Sectioning the left vagus to 32-day old rats with the left ovary in-situ resulted in lower compensatory ovarian hypertrophy than in rats with right unilateral ovariectomy. Twenty-eight or 32-day old animals with sectioning of the right vagus nerve and the right ovary in situ showed higher compensatory ovulation. Twenty-eight -day old rats with the right ovary in situ had higher progesterone and testosterone levels than animals of the same age with the left ovary in-situ. Compared to animals with the right ovary in situ, animals treated at 32-days of age, sectioning the ipsi-lateral vagus nerve resulted in higher progesterone levels. Higher progesterone levels were observed in 28- and 32 days old rats with the left ovary in situ and left vagus nerve sectioned. Thirty-two day old animals with the right ovary in situ and right vagus nerve sectioned had higher progesterone levels than rats of the same age with the left ovary in situ and left vagus nerve sectioned. Left vagotomy to 28-day old rats with the left ovary in situ resulted in higher testosterone levels, a reverse response to that observed in animals with sectioning of the right vagus and the right ovary in situ. Thirty-two day old rats with the left ovary in situ and left vagus nerve sectioned showed lower testosterone levels than animals without vagotomy and with the left ovary in situ.     

Persistence of sexual behavior in ovariectomized stumptail macaques following dexamethasone treatment or adrenalectomy

Daily administration over a period of 6 weeks of increasing doses of dexamethasone sodium phosphate (DEX) to seven long-term ovariectomized female stumptail monkeys significantly lowered circulating levels of testosterone without reducing any aspect of the females' sexual behavior or that of their male partners. Since treatment with DEX failed to suppress serum testosterone levels completely an additional experiment was performed in which the sexual behavior of five ovariectomized stumptails was compared before and after bilateral adrenalectomy, combined with chronic administration of both gluco- and mineralocorticoids. Serum levels of both testosterone and estradiol were reduced to very low levels in females after ovariectomy and adrenalectomy, yet no significant depression of females' sexual performance or that of their male partners occurred. Subsequent sc administration of estradiol or estradiol + testosterone in Silastic capsules to ovariectomized, adrenalectomized stumptails had little effect on sexual interaction. In a third experiment five ovariectomized stumptails which initially were relatively unreceptive and unattractive to males were given first testosterone and then testosterone + estradiol sc in Silastic capsules. One of the three indexes of females' receptivity increased significantly after testosterone; however, no other essential aspect of sexual interaction was affected. These findings suggest that sex steroids are normally not required in the female stumptail macaque for activation of preceptive and receptive sexual behaviors or for maintenance of sexual attractivity.     

The influence of estradiole and tibolone administration on leptin levels in women with surgically induced menopause

Background: Several studies suggest that changes in estrogens and androgens during menopause play a role in the regulation of leptin production. Some authors present hypothesis that sex hormone replacement therapy can modulate leptin levels but up to date evidence shows that the influence of endogenous estrogens, androgens levels and sex hormone therapy on leptin concentration remains uncertain. Aim: To evaluate the influence of surgically induced menopause on serum leptin levels and the influence of different types of hormonal therapy on serum leptin concentrations. Methods: 58 women with surgically induced menopause were divided into three groups. Women who did not receive any hormonal substitution (group 1), women who received Estradiol l mg per day (group 2) and women who received Tibolone 2,5 mg per day (group3). The levels of leptin, estradiol, testosterone, testosterone, dehydroepiandrosterone sulfate, FSH, LH and progesterone were measured in all subjects on the 5th day and after 3 months following the surgical procedure. Results: Mean serum leptin concentrations did not differ statistically in any of the studied groups in the begining and in the end of the study. There was no correlations between serum leptin and estradiol, LH, FSH, progesterone, testosterone, free testosterone and DHEAS concentrations in any of groups before and after treatment. Conclusion: Changes in sex hormone concentrations caused by ovariectomy do not influence serum leptin concentrations. Also the short term administration of low dose estrogen therapy or tibolone in postmenopausal subjects does not change serum leptin levels.     

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.     

Action of the sexual hormones on the endogenous norepinephrine of the central nervous system (author's transl)]

The effects of ovariectomy and the injection of sexual hormones on the norepinephrine (NE) content in different areas of the central nervous system were studied in the Wistar female rat. The ovariectomy increased the NE in the hypothalamus, cerebellum and the medulla oblongata. The estradiol benzoate did not modify the NE levels in the ovariectomized rats. Progesterone decreased the NE in the hypothalamus and testosterone dipropionate increased it in the brain hemispheres. It seems possible that the hypersecretion of FSH would increase the synthesis of NE in castrated animals through the potentation of the tyroxine-hydroxylase activity. Increase in testosterone synthesis was probably responsible for the raise in NE levels. The progesterone moderated the effects of the ovariectomy, probably through feed-back mechanisms involving the hypothalamic-hypophyseal tract.     

Effects of sex hormone levels on aortic vascular reactivity and variables associated with the metabolic syndrome in sucrose-fed female rats

We studied the effect of varying levels of sex hormones, induced by ovariectomy and administration of testosterone or estradiol, on aortic reactivity in female rats with metabolic syndrome (MS) induced by a sucrose diet. Vasoreactivity of aortic rings, blood pressure, intra-abdominal fat, serum triglycerides, nitrates and nitrites, and TBARS were evaluated. Intact MS and ovariectomized MS had higher BP than intact control (C) and ovariectomized C, respectively; estradiol administration decreased BP in ovariectomized MS but not in ovariectomized C. Triglycerides and fat were both higher in MS. Triglycerides were not modified by surgery or hormone treatment, but ovariectomy increased fat. When ovariectomy was combined with hormones, however, fat was reduced to the level of intact rats. Ovariectomy decreased, but hormones increased, serum nitrates and nitrites. Vasoconstriction was larger in intact MS and ovariectomized MS + testosterone aortas than in intact C and ovariectomized C + testosterone, respectively. Vasodilation was reduced in intact MS and ovariectomized MS + testosterone compared with intact C, ovariectomized C + testosterone, ovariectomized MS, and ovariectomized MS + estradiol. The results suggest endothelial dysfunction in intact MS and ovariectomized MS + testosterone, but protection by ovariectomy + estradiol in MS due to hormones. Indomethacin reduced all contractions, but the effect was greater in estradiol-treated rats. L-NAME increased contractility, more in the ovariectomized C and MS groups and less in the estradiol-treated groups.     

Unilateral ovariectomy, flutamide treatment and HCG reverse the anovulatory action of antiprogesterone RU486 in rat.

Administration of antiprogesterone RU486 (4 mg/day) from estrus through proestrus to cyclic rats blocked ovulation. Moreover, RU486 increased basal serum concentrations of LH, PRL, testosterone and estradiol, while it decreased basal serum concentration of FSH. Both unilateral ovariectomy and antiandrogen flutamide treatment, as well as an ovulatory injection of HCG in the proestrus afternoon partially reversed, the ovulatory blockade of RU486. These results indicate that both the decreased FSH concentration and the increased testosterone concentration, as well as the reduced ovulatory LH release are responsible for the anovulatory effects of RU486.     

The influence of ovarian hormones on the rat oviductal and uterine concentration of noradrenaline and 5-hydroxytryptamine

This paper describes the effects of estradiol and progesterone on the concenirations of noradrenaline and 5-hydroxytryptamine in the Wistar rat oviduct and uterus. The levels of noradrenaline and 5-hydroxytryptamine are higher in the oviduct than in the uterus whereas p-tyrosine and tryptophan are similar in both tissues. Estradiol treatment reduced the oviductal concentration of noradrenaline but not 5-hydroxytryptamine in oviduct, while the concentrations of both noradrenaline and 5-hydroxytryptamine were reduced in uterine horn. The levels of noradrenaline in the oviduct and uterus in rats in estrus were lower than those of diestrous rats. Bilateral ovariectomy produced an increase in uterine noradrenaline and 5-hydroxytryptamine levels. These changes were reversed in the presence of ovarian hormones as indicated by experiments where unilateral ovariectomy was performed. Reserpine administration reduced noradrenaline concentration in both the oviduct and the uterus but did not change oviductal or uterine 5-hydroxytryptamine.These results indicate the existence of noradrenaline within postganglionic sympathetic nerve terminals and suggest that estrogens increase the utilization and the synthesis of noradrenaline in both the oviducts and the uterine horns. With respect to 5-hydroxytryptamine the data support the concept that it is mainly associated with mast cells.     

Influences of retrochiasmatic surgical transection on mating and serum ovarian hormone levels in the androgenized rat

In previous studies female rats were shown to increase mating after retrochiasmatic surgical transections prior to ovariectomy and after ovariectomy with and without hormone replacement. This study was designed to determine if retrochiasmatic surgical transections (FC) or sham-FC would produce similar increased mating in androgenized rats. Four of thirty-one (13%) testosterone propionate (TP)-treated rats showed minimal mating without surgery, and 27 (87%) failed to mate. Mating occurred up to 30 days following FC, whereas temporary mating resulting from sham-FC had declined to presurgical levels by 30 days after surgery. Mating after ovariectomy was not facilitated by daily injections of 0.2μg of estradiol cypionate, but was facilitated after daily injections of 1.6 μg. TP-treated rats with FC showed more mating after 1.6 μg estradiol cypionate injections than the sham-FC and non-TP-treated controls. Serum estradiol-17β and progesterone levels at autopsy did not differ between TP-treated rats mating without surgery and those failing to mate. TP-treated rats with sham-FC surgery showed levels of estradiol-17β and progesterone similar to those of nonsurgical TP-treated rats and were combined into a single control group for comparison to the FC group. Serum levels of estradiol-17β did not differ between the control and FC group, whereas serum progesterone levels were decreased in the FC group. Serum levels of estradiol-17β and progesterone in TP-treated rats without FC were similar to baseline levels observed in this colony during the 4-day estrous cycle, but were less than peak levels observed at similar times on proestrus and diestrus Day 2, respectively. One possible effect of early androgen treatment would be to initiate a sustained inhibitory input to the mediobasal hypothalamus from the septal-preoptic area regions, thus causing deficits in mating. The lordosis responding in the androgenized rat after surgical interruption of the preoptic area-anterior hypothalamic continuum suggests that an inhibitory input was disrupted. It was further suggested that the higher mating observed in the FC group compared to the sham-FC group was not the result of higher ovarian hormone levels.     

Further investigation of the role of progesterone in the control of embryo transport in the mouse

Combined ovariectomy and adrenalectomy retarded mouse embryo transport while either operation alone did not. Serum progesterone levels were reduced after ovariectomy and after the combined operation but detectable levels were still present on Day 4 following both procedures. Embryo transport was also retarded after administration of testosterone propionate. This effect was abolished by progesterone and was not mimicked by 5 alpha-dihydrotestosterone. From these results it is concluded that progesterone influences embryo transport and that androgenic effects are probably a result of antagonism of progesterone.     

Effect of striatum destruction on the hypothalamo-pituitary-adrenal axis function in adrenalectomized rats

The influence of the bilateral striatectomy on activation of the hypothalamus-pituitary-adrenal axis after unilateral adrenalectomy was investigated. Increasing of the intact adrenal gland's mass in striatectomized rats was less than in the control group. It was combined with decreasing of the production of corticosteroids by intact gland. Such disturbances were more obvious in rats with destruction of the dorsal striatum than the ventral one. These facts suggest the striatum participation, its dorsal zone in particular, in the processes of regulation of the hypothalamus-pituitary-adrenal axis.     

Estradiol induces and progesterone inhibits the preovulatory surges of luteinizing hormone and follicle-stimulating hormone in heifers

Objectives were to determine: 1) whether estradiol, given via implants in amounts to stimulate a proestrus increase, induces preovulatory-like luteinizing hormone (LH) and follicle-stimulating hormone (FSH) surges; and 2) whether progesterone, given via infusion in amounts to simulate concentrations found in blood during the luteal phase of the estrous cycle, inhibits gonadotropin surges. All heifers were in the luteal phase of an estrous cycle when ovariectomized. Replacement therapy with estradiol and progesterone was started immediately after ovariectomy to mimic luteal phase concentrations of these steroids. Average estradiol (pg/ml) and progesterone (ng/ml) resulting from this replacement were 2.5 and 6.2 respectively; these values were similar (P greater than 0.05) to those on the day before ovariectomy (2.3 and 7.2, respectively). Nevertheless, basal concentrations of LH and FSH increased from 0.7 and 43 ng/ml before ovariectomy to 2.6 and 96 ng/ml, respectively, 24 h after ovariectomy. This may indicate that other ovarian factors are required to maintain low baselines of LH and FSH. Beginning 24 h after ovariectomy, replacement of steroids were adjusted as follows: 1) progesterone infusion was terminated and 2 additional estradiol implants were given every 12 h for 36 h (n = 5); 2) progesterone infusion was maintained and 2 additional estradiol implants were given every 12 h for 36 h (n = 3); or 3) progesterone infusion was terminated and 2 additional empty implants were given every 12 h for 36 h (n = 6). When estradiol implants were given every 12 h for 36 h, estradiol levels increased in plasma to 5 to 7 pg/ml, which resembles the increase in estradiol that occurs at proestrus. After ending progesterone infusion, levels of progesterone in plasma decreased to less than 1 ng/ml by 8 h. Preovulatory-like LH and FSH surges were induced only when progesterone infusion was stopped and additional estradiol implants were given. These surges were synchronous, occurring 61.8 +/- 0.4 h (mean +/- SE) after ending infusion of progesterone. We conclude that estradiol, at concentrations which simulate those found during proestrus, induces preovulatory-like LH and FSH surges in heifers and that progesterone, at concentrations found during the luteal phase of the estrous cycle, inhibits estradiol-induced gonadotropin surges. Furthermore, ovarian factors other than estradiol and progesterone may be required to maintain basal concentrations of LH and FSH in heifers.     

Evidence that the anterior hypothalamus contributes to the control of tonic secretion of follicle-stimulating hormone in the female rat

A horizontal knife cut was placed between the dorsal anterior hypothalamic area (DAHA) and the medial basal hypothalamus to examine the role of the DAHA in the selective secretion of follicle-stimulating hormone (FSH) following unilateral ovariectomy (ULO) and bilateral ovariectomy of the rat. Complete cuts markedly attenuated the increase in FSH observed 8 h after ULO, whereas incomplete or sham cuts did not. Concentration of luteinizing hormone (LH) did not increase in any group. These cuts also blocked the prolongation of estrous FSH secretion observed in long-term hemicastrated rats, since FSH levels on estrus were significantly lower in rats with complete cuts than in those rats given sham or incomplete cuts. In contrast, neural surgery had no effect on proestrous FSH concentrations. Finally, when FSH levels were monitored 2 days after bilateral ovariectomy, the postcastration rise in FSH was not altered by any neurosurgical procedures. These results support the hypothesis that a neural system originating in, or passing through, the DAHA is necessary for the selective increase in FSH following ULO.     

Testosterone and sexual experience alter levels of plasma membrane binding sites for progesterone in the male rat brain.

Physiological levels of progesterone act in conjunction with androgens to facilitate copulatory behavior in male rats, mice, and lizards. Radiolabeled progesterone conjugated to bovine serum albumin measured specific binding sites in membrane fractions from male rats that were gonadectomized and testosterone treated, or remained gonadally intact, to determine the role of gonadal steroids on mPR binding. To determine whether behavioral experience could alter binding levels, males either remained sexually na?ve or became sexually experienced. In sexually na?ve males, the highest levels of specific binding occurred in the dorsal portions of the medial preoptic area, with only moderate levels of binding in ventral portions of the medial preoptic area and the dorsal and ventral medial hypothalamus. However, conjugated progesterone binding in these brain regions did not change as a function of testosterone or behavioral manipulations. In contrast, the amygdala responded to behavioral experience with significantly (4-fold) increased binding in gonadectomized, T-treated males with sexual experience. These data indicate that the neuronal plasticity for membrane-associated progesterone binding is regionally specific, being regulated by sexual experience following the reinstatement of testosterone levels, thus suggesting a functional role for plasma membrane activity of progesterone in male rat reproduction.     

Reactivation of regressing corpora lutea by estradiol in the pregnant rat: dependence on placental lactogen

Previous investigations have clearly demonstrated that estradiol maintains corpus luteum function. However, it is unknown whether estradiol can restimulate progesterone synthesis and/or growth of corpora lutea that have already undergone luteolysis. The present study was designed to determine 1) whether estradiol can reactivate the steroidogenic capacity and/or growth of corpora lutea that are deprived of luteotropic support, 2) whether estradiol affects progesterone metabolism, and 3) whether the action of estradiol is related to levels of rat placental lactogen in the peripheral circulation. Rats were hypophysectomized and hysterectomized on Day 12 of pregnancy and were treated between Days 12 and 15 with either estradiol (100 micrograms/day) or 1-cm testosterone implants. Both treatments are known to maintain luteal concentrations of estradiol at physiological levels. In vivo treatment with either estradiol or testosterone prevented the drop in progesterone production and maintained the concentration of serum progesterone at levels found in intact pregnant rats. This action was not due to an alteration in the rate of metabolism of progesterone to 20 alpha-hydroxyprogesterone, since peripheral serum levels and in vitro production of 20 alpha-hydroxyprogesterone were unaffected by estradiol. When testosterone treatment was started 24 and 48 h after hypophysectomy and hysterectomy, at a time when progesterone production had been markedly reduced and luteal growth had ceased, a restimulation of both progesterone synthesis and luteal growth was observed. However, in all cases the ability of estradiol to stimulate progesterone was finite, and corpora lutea ceased to respond by Day 17, coincident with the time that rat placental lactogen became undetectable in the circulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

The roles of prolactin and testosterone in the development and function of granulosa lutein tissue in the rat

The luteotropic roles of prolactin and testosterone (or estradiol formed in luteal tissue) were investigated in hypophysectomized rats with homografts of granulosa lutein tissue. Using this approach, we could determine the effects of prolactin independently of estrogen, since granulosa lutein tissue does not produce estrogen de novo under these conditions. Luteinizing granulosa cells were expressed from the ovaries of immature pregnant mare's serum gonadotropin-primed Fischer 344 rats 6 h after injection of human chorionic gonadotropin. The cells were transplanted beneath the kidney capsule of adult, hypophysectomized, ovariectomized Fischer 344 recipients, which were treated with hormones daily for 12 or 14 days. In rats without treatment (no hormones, n = 3) and in rats treated with only testosterone (Silastic capsule, n = 6), only small amounts of luteal tissue (less than 5 mg/rat) were found and serum progesterone remained at low concentrations (10 ng or less) throughout the experiment. In contrast, in rats treated either with ovine prolactin (300 micrograms/day, n = 10) or with the combination of prolactin and testosterone (n = 12), serum progesterone increased to 43 ng/ml by Day 8. Beyond Day 8, serum progesterone continued to rise in rats treated with the combination of prolactin and testosterone to reach a mean value of 87 ng/ml by Day 14, and mean homograft wet weight was 49 mg/rat; in rats treated with only prolactin, serum progesterone decreased to 25 ng/ml by Day 14 and homograft wet weight was lower (24 mg/rat). Prolactin and testosterone together stimulated more homograft aromatase activity in vivo than did prolactin alone, but the in vitro production of progesterone was not different.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of the muscarinic system in regulating estradiol secretion varies during the estrous cycle: the hemiovariectomized rat model

There is evidence that one gonad has functional predominance. The present study analyzed the acute effects of unilateral ovariectomy (ULO) and blocking the cholinergic system, by injecting atropine sulfate (ATR), on estradiol (E₂) serum concentrations during the estrous cycle. The results indicate that ULO effects on E₂ concentrations are asymmetric, vary during the estrous cycle, and partially depend on the cholinergic innervation.