Ovarian Secretion Research Articles

Differential Responses of Sex Steroid Target Tissues of Rats Treated with 4-Hydroxyandrostenedione*

4-Hydroxyandrostene-3,17-dione (4-OHA) inhibits ovarian aromatase activity and causes regression of carcinogen-induced hormone-dependent mammary tumors in rats. Although estrogen levels were reduced, LH levels did not increase nor did uterine weight decline in 4-OHA-treated animals. These findings are in contrast to those in animals deprived of estrogen by ovariectomy. The possible direct action of 4-OHA on gonadotropin secretion and uterine growth was, therefore, investigated in ovariectomized rats not treated with the carcinogen. Treatment with 4-OHA for 2 weeks prevented regression of the uterus and the increase in gonadotropin secretion in ovariectomized rats in a dose-dependent manner. The effect on gonadotropin secretion of 4-OHA at 50 mg/kg.day was similar to that of dihydrotestosterone at 0.5 mg/kg.day and could be completely antagonized by administration of the antiandrogen flutamide. The stimulation of uterine growth by 4-OHA was also blocked by flutamide, but not by the antiestrogen enclomiphene. The trophic action of 4-OHA at 50 mg/kg.day was equivalent to that of 1.8 mg/kg.day dihydrotestosterone. Furthermore, treatment with 4-OHA caused a reduction in uterine estrogen receptor and progesterone receptor levels. The reduction in uterine estrogen and progesterone receptor levels was also counteracted by the concomitant injection of flutamide, but not by enclomiphene. The results suggest that in the rat 4-OHA has multiple actions on sex steroid target tissues in addition to inhibition of aromatase. The effects appear to be related to the androgenic rather than estrogenic activity of the compound. Inhibition of gonadotropins may help maintain reduced ovarian estrogen secretion and contribute to the antitumor activity of this compound.

Suppression of postmenopausal ovarian steroidogenesis with the luteinizing hormone-releasing hormone agonist goserelin.

Twenty-one postmenopausal women with advanced breast cancer were treated with monthly 3.6-mg sc injections of the LHRH agonist goserelin [D-Ser-(But)6, Azgly10-LHRH] to determine whether the resultant endocrine changes could provide an explanation for the clinical responses that occur during therapy with this agent. After 4 weeks, serum gonadotropin levels were less than 10% of pretreatment levels, whereas serum PRL levels did not change. A significant decrease in serum testosterone occurred in 19 of 20 patients; this fall was associated with a 22% fall in serum estradiol levels. Serum androstenedione levels also decreased, but serum estrone and dehydroepiandrosterone sulfate (DHAS) levels did not. The lack of fall in serum DHAS levels indicates that the changes in androgen levels were a result of reduced ovarian secretion, and the reduced estradiol levels were a consequence of reduced precursor (i.e. testosterone) availability. The continued dependence of ovarian androgen secretion on gonadotropin stimulation after the menopause may explain the responses of some patients to LHRH agonists and some other therapeutic agents of unknown or uncertain modes of action.

Analysis of release of porcine relaxin by reverse haemolytic plaque assay: evidence for autoregulation.

Relaxin release from monodispersed luteal cells derived from pregnant pigs (days 100-110 of gestation; n = 3) was detected by a reverse haemolytic plaque assay. In this technique, luteal cells were co-cultured in monolayers with ovine erythrocytes coupled to protein-A. In the presence of porcine relaxin antiserum and complement, a zone of haemolysis--a plaque--developed around relaxin-releasing luteal cells. Luteal cells were preincubated with porcine relaxin (up to 1000 ng/ml) or progesterone (up to 0.5 micrograms/ml) for 18 h before the plaque assay. Relaxin (but not progesterone) pretreatment inhibited subsequent relaxin release. The inhibitory effect of relaxin on its own release (autoregulation) has the potential to be a significant part of the local mechanisms which contribute to the overall control of ovarian secretion of protein hormones.

The source(s) of estrogen production in hirsute women with polycystic ovarian disease as determined by simultaneous adrenal and ovarian venous catheterization

To determine the significant source(s) of estrogen production in women with polycystic ovarian disease (POD), 12 women underwent selective adrenal and ovarian vein catheterization, with simultaneous peripheral blood samplings for determination of cortisol, androstenedione (delta 4A), testosterone, estrone (E1), and estradiol (E2). Ovarian vein E2 gradients were observed in 11 of the 12 patients with a mean of 13.4, whereas adrenal blood samples did not demonstrate significant E2 gradients. Seven of 8 patients exhibited ovarian secretion of E1, with a mean gradient of 13.6 times that of peripheral blood, whereas 4 of the 8 adrenal samples showed E1 gradients. The mean value was 1.4 times peripheral levels. No significant correlations were found between peripheral E1 levels and body weight or degree of adiposity, nor was there a relationship between obesity and E1/delta 4A molar ratio in peripheral blood. The subjects with the highest ovarian delta 4A levels had a significant correlation between peripheral delta 4A and E1. Therefore, our data indicate a significant contribution of ovarian E1 secretion to the peripheral E1 pool in addition to the extraglandular conversion of delta 4A to E1. There was general lack of correlation between peripheral E1 concentrations and plasma E2, and these relationships versus body size suggest that the major source of E2 in women with POD was ovarian secretion.

Effect of gonadal activity on the cranial dimorphism of the rat.

Weanling rats of both sexes were submitted to either castration, or castration together with periodic injections of testicular extract to males or of ovarian extract to females. Control and experimental animals were sampled at 63 days of age. Cranial differentiation between sexes was estimated by Mahalanobis D2 distances. The controls showed a significant sexual cranial difference. Orchidectomy decreased cranial differences and this effect was compensated by injections of testicular extract. On the other hand, oophorectomy increased cranial differences, which were diminished by injections of ovarian extract. Sexual cranial dimorphism in the normal rat seems to be the result of a counteracting effect between testicular and ovarian hormonal secretions.

Peripheral progesterone concentrations in the luteal-phase ewe: effects of a beta-adrenergic receptor antagonist and two beta 2-adrenergic agonists.

Peripheral blood samples were collected at 10-min intervals from three conscious sheep in which ovulation had been induced 6-10 days previously using exogenous hormones. Saline was infused into a jugular vein for about 1 h, followed by the experimental drug for 1-2 h and followed by saline again for a further 2 h. The experiments were repeated following induced luteolysis and ovulation. The infusion of a beta-adrenergic antagonist (propranolol) into three conscious luteal-phase ewes decreased (P less than 0.05) the peripheral progesterone concentration in each animal. Infusions of beta 2-adrenergic agonists (ritodrine and salbutamol) increased (P less than 0.05) the progesterone concentration in four out of eight experiments. The beta-adrenergic antagonist decreased the heart rate and the beta 2-adrenergic agonist increased it; the arterial blood pressure and respiratory rate were unaffected. The decrease in the progesterone concentration in response to the beta-adrenergic antagonist suggests that the normal ovarian secretion of progesterone is partly the result of sympathetic stimulation, and that the sympathetic innervation of the ovary may have a physiological role in modulating progesterone secretion.

Fertility and hormonal responses to temporary relief of heat stress in lactating dairy cows

The influence of temporary cooling on pregnancy rate and ovarian secretion of cortisol, estradiol and progesterone in Holstein cows was evaluated during the months of June to September. Cows were randomly assigned to one of five treatment groups: 1) evaporative cooling, 8 d; 2) evaporative cooling, 16 d; 3) refrigerated air conditioning, 8 d; 4) refrigerated air conditioning, 16 d and 5) controls maintained outdoors with access to shade. Estrus was synchronized by giving two injections of prostaglandin (25 mg). Cows in the cooled groups were placed in box stalls at the time of the second prostaglandin injection, allowing them to be cooled for approximately 3 d prior to breeding. Blood samples were taken on days 0, 5, 10, 15, 20 and 25 postbreeding and serum was analyzed for estradiol, cortisol, progesterone and a pregnancy-specific protein. Pregnancy rates as determined by palpation per rectum at 40 to 60 d post breeding were not different between cows in cooled treatments, regardless of duration or type of cooling. Pregnancy rate was higher (P<0.05) in cooled as compared to control cows. Serum progesterone concentrations were higher on Day 15 in cooled cows as compared to control cows. No differences in serum estradiol or cortisol concentrations were observed between cooled and control cows. Pregnancy-specific protein determinations indicated that 50% of both cooled and control cows conceived. Results indicate that temporary cooling increased pregnancy rates by increasing embryonic survival rates.

Ovarian influence on uterine growth in prepubertal gilts.

A determination of age of the prepubertal gilt at which ovaries affect uterine growth is necessary before establishing the extent to which length of uterus is influenced by inherent differences, as opposed to those due to ovarian secretions. In Exp. 1 and 2, the effect of presence of ovaries on uterine growth was determined following ovariectomy in 186 crossbred gilts. The uterus was examined 40 or 80 d after ovariectomy for length, weight and diameter. Growth of uterine horns in gilts from 20 to 60 d of age was equal with or without ovaries. Uterine horns in ovariectomized gilts continued to grow slowly from 60 to 140 d of age and then remained static to 180 d of age. Uterine horns in gilts with ovaries increased rapidly in length, weight and diameter, with concomitant increase in ovarian weight between 100 and 180 d of age. In Exp. 3, uterine growth and ovarian compensation after unilateral ovariectomy and hysterectomy at 60 d of age were determined in 85 crossbred gilts from 60 to 180 d of age to evaluate the unilateral ovariohysterectomy model for studying association of uterine length before puberty and subsequent uterine capacity. In response to removal of an ovary and a uterine horn, the remaining ovary compensated, but the remaining uterine horn did not. This study demonstrated that the ovaries did not influence uterine growth until after 60 d of age and that unilateral ovariohysterectomy could be performed as early as 60 d of age without altering consequent normal uterine growth.

Inverse seasonal relationship between melatonin and ovarian activity in humans in a region with a strong seasonal contrast in luminosity.

The effects of season on the activity of the pituitary-ovarian axis and the pineal gland were studied in 11 women by serum and urinary melatonin determinations and in 21 women by measurements of the serum concentrations of anterior pituitary and ovarian hormones during the dark and light seasons. A melatonin index was determined by integration of the area below the curve of serum melatonin concentrations during 24-h periods in both seasons. During the dark season, the daytime 12-h melatonin index and daytime urinary melatonin excretion were significantly higher than during the light season. In addition, the duration of the nocturnal melatonin pulse (serum melatonin levels, greater than 65 pmol/L) was lengthened during this season, whereas the mean serum estradiol concentration was significantly decreased at the time of ovulation and during the luteal phase of the cycle, indicating lowered ovarian activity. Luteal phase gonadotropin concentrations were increased during the dark season, which was also characterized by increased sex hormone-binding globulin (SHBG) and decreased free testosterone concentrations and free androgen indices (ratio of testosterone to SHBG X 700) throughout the menstrual cycle. The dark season was thus characterized by increased melatonin secretion and decreased ovarian and androgenic activities. In summary, we characterized two season-dependent hormonal phenomena. Although we did not prove any cause and effect association between melatonin and anterior pituitary-ovarian hormones, the inverse seasonal relationship in pineal gland and ovarian secretion suggests that melatonin is causally related to reproduction in humans.

Secretion of androgens and estrogens by normal and neoplastic ovaries in postmenopausal women

Peripheral and ovarian venous concentrations of testosterone, androstenedione, estradiol-17 beta, and estrone were measured in 30 postmenopausal women. Ovarian venous concentrations of testosterone and estradiol-17 beta were 5.6 and 4.3 times the peripheral concentrations of women with normal ovaries. This suggests that the ovaries of postmenopausal women continue to secrete these two steroids. Mean peripheral testosterone concentrations in 14 postmenopausal women with a nonfunctional or functional ovarian tumor were increased significantly. Ovarian venous concentrations of these four steroids from the side draining the tumor-bearing ovary were increased in 40 to 80% of the women. The venous concentrations from the normal ovary were also increased in 22% or more of the women with an ovarian tumor. Any ovarian neoplasm in postmenopausal women may be associated with increased ovarian sex-steroid secretion.

Vasoactive Intestinal Peptide Regulates Cholesterol Side-Chain Cleavage Cytochrome P-450 (P-450scc) Gene Expression in Granulosa Cells from Immature Rat Ovaries

Vasoactive intestinal peptide (VIP), a neuropeptide present in ovarian nerves, has been previously shown to induce synthesis of the side-chain cleavage cytochrome P-450 enzyme which catalyzes the conversion of cholesterol to pregnenolone (the rate-limiting step in progesterone synthesis). In the present study we demonstrate, by means of a bovine 3'-specific P-450scc cDNA probe, that this VIP effect is exerted at least partially at the level of gene expression in cultured granulosa cells that were isolated from estrogen-primed, immature rats. The size and level of the 2.0 kilobase P-450scc mRNA species was assessed by Northern blot analysis, while the translatability of this mRNA was assayed by immunoisolation of the 35S-labeled P-450scc precursor protein translated from total RNA of control and stimulated granulosa cells. FSH was much more effective than VIP at increasing P-450scc mRNA concentrations in cultured granulosa cells, whereas secretin treatment was ineffective. The results suggest that, like FSH, the stimulatory effect of the neuropeptide VIP on ovarian progesterone secretion involves regulation of P-450scc gene expression during functional maturation of the prepubertal ovary.

Involvement of postnatal gonads in the maturation of dopaminergic regulation of prolactin secretion in female rats.

Permanent effects of postnatal gonads on dopamine (DA)-mediated regulation of PRL secretion were examined in adult female rats of the Wistar-Imamichi strain. Experiments were uniformly done at the age of about 10 weeks. First, rats were bilaterally ovariectomized on varying postnatal days, i.e. 24 h after birth [neonatal castration (NC)] or at 1, 2, 3, 4, or 6 weeks of age. Intact diestrous females were also examined. All groups were injected ip with saline or sulpiride (1 mg/kg BW), and blood samples were collected by rapid decapitation 20 min later. Also, in saline control groups, the anterior pituitary (AP) PRL content was determined. In NC females, significant PRL release was not observed by either sulpiride or saline. However, stimulation of PRL release by sulpiride was observed consistently in rats ovariectomized on or after 1 week of age. Although there was not a complete correlation between the plasma PRL level attained after sulpiride treatment and the AP PRL content, the general trend was that the AP PRL content was increased as the postnatal age of the ovariectomy was delayed. Values in intact adult females exceeded those in all of the castrated groups in both parameters. Second, daily sc injection for 7 days with estradiol benzoate (E2; 2.5 micrograms/kg BW) and/or progesterone (P; 5 mg/kg BW) was given after NC to determine which ovarian secretion(s) is involved in the aforementioned findings. Sulpiride stimulated PRL release in NC females that had been treated neonatally (postnatal days 3-9) with either E2 or P. This effect was accompanied by an increase in the AP PRL content. An enhancement of both parameters was also observed when the same dose of E2 or P was given in the fourth week (postnatal days 22-28). However, neither parameter was further augmented by concurrent administration of E2 and P at either postnatal time. Characteristics of AP DA receptors were subsequently analyzed in some of the foregoing groups using [3H]spiperone. The number of binding sites, when expressed as femtomoles per pituitary, did not differ among all groups examined. However, a significant difference in the dissociation constant (Kd) was observed between NC females and females castrated at 6 weeks of age. The Kd in NC females was not altered by subsequent neonatal treatment with E2 and/or P. Nonetheless, the E2 effect on Kd was dependent on when E2 was given after NC.(ABSTRACT TRUNCATED AT 400 WORDS)

Persistence of Insulin Resistance in Polycystic Ovarian Disease after Inhibition of Ovarian Steroid Secretion

Six nonobese women with polycystic ovarian disease (PCOD) showed significant hyperinsulinemia, compared with controls after oral glucose (P less than 0.05). As an indicator of insulin sensitivity, in vitro proliferation of erythrocyte progenitor cells of PCOD subjects exposed to physiologic concentrations of insulin was significantly blunted (P less than 0.001). Monocyte insulin receptor binding was not impaired in the PCOD subjects. Three of the PCOD patients were treated with a long-acting gonadotropin-releasing hormone agonist for 6 months, which resulted in marked suppression of ovarian androgen secretion but no demonstrable changes in in vivo or in vitro indicators of insulin resistance. Thus insulin resistance in PCOD subjects appears to be unrelated to ovarian hyperandrogenism (or acanthosis or obesity). Although certain tissues are insulin-resistant in PCOD patients, the ovary may remain sensitive and overproduce androgens in response to high circulating insulin levels.

Placental-ovarian relationship in the control of testosterone secretion in the rat.

Both ovaries and placentae of rats produce androgen in the second half of pregnancy. The objectives of this investigation were to determine whether the pituitary controls both ovarian and placental secretion of testosterone, to find out whether ovarian secretion of testosterone is maintained by the placenta, and to examine whether levels of testosterone produced by the ovaries and placentae depend upon the number of placentae present. Pregnant rats were hypophysectomized with or without hysterectomy in one experiment, and hypophysectomized with or without partial hysterectomy leaving one placenta in situ in another experiment. Testosterone output by the placenta(e) or the ovary was quantified. The results suggest that placental secretion of testosterone is independent of the pituitary between days 12 and 18 of pregnancy, reduction in placental number causes the remaining placenta to compensate by increasing its testosterone output, and ovarian secretion of testosterone may be under placental control between days 12 and 18 of pregnancy.

Age-associated increases in serum follicle-stimulating hormone levels on estrus are accompanied by a reduction in the ovarian secretion of inhibin.

In light of recent data demonstrating age-related alterations in the secretion and production of follicle-stimulating hormone (FSH) during the secondary FSH surge on estrus, the following study was conducted to determine the effects of age on periovulatory inhibin secretion. Ovarian venous blood was collected from groups of ether-anesthetized 3- and 7-month-old rats exhibiting 4-day estrous cycles at the following times: 1200 and 2400 h on proestrus and 1600 h on estrus. Following a 10-min collection period, a terminal blood sample was obtained from the abdominal aorta. Peripheral serum concentrations of luteinizing hormone (LH), FSH, estradiol-17 beta (E2), progesterone (P) and testosterone (T) were measured by RIA. Inhibin activity in ovarian venous serum (OVS) was assessed by the ability of OVS to suppress basal FSH secretion from dispersed pituitary cells during a 24-hour culture period. At 1200 h on proestrus, serum FSH (and LH) levels were higher in 7-month-old rats than in younger rats while the FSH-suppressing activity of OVS did not differ between age groups at this time. Bioassayable inhibin activity substantially declined between 1200 and 2400 h on proestrus in both groups. By 1600 h on estrus, serum FSH levels and inhibin secretion were higher and lower, respectively, in the older age group compared to 3-month-old rats. Significant increases in inhibin secretion between 2400 h on proestrus and 1600 h on estrus were observed only in younger rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Cimetidine-induced prolactin release in rats. The effect of sex and gonadal steroids.

The cimetidine-induced plasma Prl response was examined in rats of both sexes. First, 10 week old intact adult males and females (dioestrous) were compared. There was no significant difference in the Prl response to cimetidine between the two groups, despite the fact that in adult females the anterior pituitary Prl content was 4 times greater than in males. Second, the effect of gonadal state in adult age on the Prl response to cimetidine was examined in both sexes. In male rats, gonadectomy at the age of 6 weeks significantly reduced the plasma Prl response as well as the pituitary Prl content, both of which were sufficiently restored by testosterone replacement. However, in females, neither gonadectomy at the age of 6 weeks nor subsequent oestradiol replacement affected the Prl response to cimetidine, despite the fact that gonadectomy significantly reduced and oestradiol treatment significantly enhanced the pituitary Prl content. Third, possible permanent effects of the postnatal gonadal milieu on the cimetidine-induced Prl response and the pituitary Prl content were examined in both sexes by castration at varying postnatal ages. The ratio of plasma Prl response to pituitary Prl content was similar in all castrated males. In females, however, the ratio decreased with increasing castration age. In conclusion, the mechanism of cimetidine-induced Prl release is less sex-dependent than are the mechanisms of Prl release by other Prl secretagogues. First, this may be due to a minor role of oestrogen in females in determining the Prl response to cimetidine. Second, the postnatal ovarian secretions may exert a permanent inhibition of the development of the cimetidine-mobilized anterior pituitary Prl pool.

Aging of the hypothalamo-pituitary-ovarian axis: Hormonal influences and cellular mechanisms

Longitudinal studies employing heterochronic ovarian grafts and long-term ovariectomy indicate that there is no single pacemaker of reproductive aging. Neuroendocrine dysfunction, the declining follicular reserve, and ovarian secretions all contribute to reproductive decline, and their relative importance to the different stages of reproductive aging varies markedly. Moreover, although ovarian secretions during adulthood potentiate certain aspects of the reproductive aging process, their behavior does not fit a simple model of cumulative steroidal damage incurred over the lifespan. Current data are more consistent with temporally distinct windows of steroidal vulnerability for the events affected: cycle lengthening is affected by ovarian secretions during the period of cyclicity, and post-cyclic neuroendocrine failure is potentiated by ovarian secretions during the peri- and post-cyclic period of the lifespan. Recent examination of estradiol receptor dynamics reveals multiple, albeit selective, changes during aging that may contribute to the age-related impairments of tissue sensitivity to estrogen. These changes vary qualitatively and quantitatively among target tissues. Thus, aging of the hypothalamo-pituitary-ovarian axis at the cellular level mirrors, in its multifactorial nature, aging at the organismic level.

Diurnal progesterone rhythms in the female mouse.

The patterns of peripheral progesterone concentrations were investigated in a number of murine models on a 13 h light: 11 h darkness lighting regime. The pattern in the intact mouse at dioestrus was compared with that in the ovariectomized mouse. A diurnal pattern was recorded in both, maxima occurring around the end of the light period; no conspicuous nadir was recorded, levels of progesterone remaining relatively constant over a 14-h period. Adrenalectomized mice displayed no such rhythm, indicating that the adrenal is responsible for any diurnal rhythm in peripheral plasma progesterone concentrations at dioestrus. At pro-oestrus in intact animals a similar rhythm was observed, but the maximum levels of progesterone were approximately five times greater than at dioestrus and, moreover, persisted in adrenalectomized mice, indicating that the rhythm of adrenal secretion of progesterone is masked by ovarian secretion. Ovariectomized mice with implants of oestradiol-17 beta displayed a similar rhythm to that of intact mice at dioestrus, but had significantly higher plasma progesterone levels around the time of the maxima although not over the total 24-h period. An s.c. injection of oestradiol benzoate superimposed on oestrogen levels produced by implants had no significant effect on plasma progesterone levels. Also at pro-oestrus the pattern of peripheral LH concentration was investigated in both the intact and the adrenalectomized mouse. For both, maxima were recorded just before darkness, at 19.00 h, in advance of the progesterone surge. In adrenalectomized mice this surge at 19.00 h was attenuated. The possible role of adrenal progesterone in ovulation and the mechanisms by which endogenous oestrogens might enhance adrenal progesterone output are considered.

Ovarian steroid production in rats treated with gonadotropin-releasing hormone during early pregnancy

In the pregnant rat, luteinizing hormone (LH) stimulates the ovarian production of testosterone (T) which is aromatized to estradiol (E 2). E 2 promotes progesterone (P) synthesis by the ovary. To determine if the administration of gonadotropin-releasing hormone (GnRH) disrupts pregnancy by suppressing ovarian steroid production, rats were treated on days 7–12 of pregnancy with 25, 50 or 100 μg/day of GnRH or 0.2, 1 or 5 μg/day of a GnRH agonist (GnRH-Ag). The higher two doses of GnRH or GnRH-Ag within 24 h suppressed peripheral levels of plasma P and terminated pregnancy within 48 h. By day 12, P levels in the ovarian vein in rats treated with GnRH or GnRH-Ag in respective doses were 2098 ± 261, 732 ± 437,110 ± 15, and 2575 ± 463,49 ± 9,43 ± 8 compared to 1833 ± 433 ng/ml in controls. Daily treatment of P (4mg) and E 2 (0.5 μg) simultaneously with GnRH-Ag at its maximum dose reversed the abortifacient effect of GnRH-Ag and maintained pregnancy. Peripheral levels of Plasma LH in all groups were higher than controls on days 10 and 12. Ovarian vein levels of T on days 10 or 12 of pregnancy were either not significantly different from controls (at 2703 ± 607 or 3249 ± 690 pg/ml, respectively) or increased dramatically to 9547 ± 1769 on day 10 and to 5985 ± 1426 pg/ml on day 12 in rats treated with 0.2 μg of GnRH-Ag. Similarly, ovarian vein levels of E 2 on days 10 or 12 were either not significantly different from controls (at 2022 ±227 or 2793 ± 184 pg/ml, respectively) or increased dramatically to 2980 ± 58 pg/ml on day 10 in rats treated with 25 μg of GnRH or to 3296 ± 241 on day 10 and to 3420 ± 325 pg/ml on day 12 in rats treated with 0.2 μg of GnRH-Ag. These results indicate that the abortifacient effect of GnRH administration in rats is not due to its effect on the uterus, but to its suppressive effects on ovarian P secretion. There was no evidence to show that a GnRH-induced fall in ovarian secretion of either T or E 2 were involved in this process.

Dissociation between the ovarian factors controlling sexual receptivity and preovulatory secretion of LH in cyclic female rats.

Ovariectomy and treatment with oestradiol benzoate (10 micrograms OB) on the day before behavioural oestrus eliminated the preovulatory surge of LH and reduced the level of sexual receptivity on the following day. Sexual behaviour, but not the LH surge, was restored by progesterone (0.5 mg) given 18 h later. Injection of OB on the day after behavioural oestrus induced a small release of LH and normal sexual behaviour on the following day. Ovariectomy on the day after behavioural oestrus reduced the stimulatory effect of OB on sexual behaviour and eliminated its weakly stimulatory effect on LH release. Sexual behaviour, but not the small LH surge, was restored in these animals by progesterone (0.5 mg) given 18 h later. Treatment of rats ovariectomized 2 days before the day of the LH surge with implants containing oestradiol or injections of oestradiol (1 microgram) induced LH surges but the amplitudes of these LH surges were much smaller than those of the normal LH surge. Treatment of intact rats with OB increased serum progesterone levels 24 h later, an effect which was eliminated by ovariectomy. Injections of LH (20 micrograms) into intact rats on the day after behavioural oestrus also increased serum progesterone concentrations but failed to stimulate sexual behaviour. It is suggested that OB treatment of intact rats on the day after behavioural oestrus stimulates sexual behaviour by inducing a surge of LH secretion which activates ovarian secretion of progesterone. Thus, oestrogen and progesterone but not the LH surge are essential for sexual behaviour.(ABSTRACT TRUNCATED AT 250 WORDS)