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Responses of plasma "estradiol" and plasma LH to ovariectomy, ovariectomy plus adrenalectomy, and estrogen injection at various ages.

Plasma LH and "estradiol" were measured by radioimmunoassay in female rats 5, 10, 15, 20, 25, 30, 40, and 80 days of age, and the changes in these hormone levels 24 h after ovariectomy, ovariectomy plus adrenalectomy, and estrogen injection were determined. Plasma "estradiol" was high at 5 days of age; it increased further to a peak at 15 days of age, and declined thereafter to the low levels seen in adult rats. At each age, plasma "estradiol" declined about 50% 24 h after ovariectomy, whereas it fell to undetectable levels 24 h after ovariectomy plus adrenalectomy at 20 and 80 days of age. Plasma LH did not increase 24 h following ovariectomy at 5 days of age, but it did at all ages thereafter. The peak increase occurred 24 h after ovariectomy at 15 days of age, and the increment was progressively smaller at older ages. Ovariectomy plus adrenalectomy did not cause a significantly greater increase in plasma LH than ovariectomy alone. Injection of estradiol caused a decrease in plasms LH at all ages except in the animals ovariectomized at 5 days of age. The greatest decrease was seen in animals ovariectomized at 15 days of age, with a progressively smaller negative feedback response as age increased. In addition to providing systematic data on changes in the negative feedback effect of estradiol at various ages, the results indicate that, especially in immature animals, there is a circulating substance which cross-reacts with antibodies to estradiol but which does not appear to be a biologically-active estrogen. It does not come from the ovaries and disappears from the circulation if the adrenals as well as the ovaries are removed.

Adrenal Glands

The conversion of an ovariectomy-nonresponsive to an ovariectomy-responsive mammary tumor strain.

MTW9, a transplantable mammary tumor in Wistar Furth rats, shows little growth unless host serum prolactin is increased. This study compares the response to ovariectomy of MTW9-MtT, a tumor developed in rats bearing the mammosomatotropic tumor MtTW10 (serum prolactin 500 to 7000 ng/ml) with MTW9-P developed in rats given chronic perphenazine treatment (4 mg/kg/day). Serum prolactin concentrations were 150 to 600 ng/ml in MTW9-P bearing rats. MTW9-MtT does not regress after ovariectomy but does regress after surgical removal (resection) of MtT. Ovariectomy plus MtT resection leads to greater tumor regression than MtT resection alone. MTW9-P does not regress when perphenazine administration is stopped but does regress after ovariectomy, whether or not rats are given perphenazine. Administration of estradiol (10 mug/day) to rats with complete ovariectomy-induced regression of MTW9-P results in regrowth of tumor. These data suggest that MTW9-P may represent a clone of MTW9 with a lower requirement for prolactin.

Animals

Prolactin binding in ovariectomy-responsive and ovariectomy-nonresponsive rat mammary carcinoma.

Growth of the transplantable mammary tumor, MTW9, in W/Fu rats is greatly enhanced by elevated serum prolactin concentrations. This report compares the prolactin binding to tumor membranes in two mammary tumor strains derived from MTW9. Maximum binding to membranes of both tumors occurred at pH 7.6 after incubation for 30 hr at 4 degrees. The binding was inhibited only by polypeptide hormones that possess lactogenic activity. MTW9-P, an ovariectomy-responsive tumor developed in rats maintained on daily perphenazine injections, had 4-fold-higher prolactin binding than had MTW9MtT, an ovariectomy-nonresponsive tumor developed in rats bearing the mammosomatotropic pituitary tumor, MtTW10. Withdrawal of perphenazine from rats bearing MTW9-P caused a fall to normal of plasma prolactin, no tumor regression, and no significant change in prolactin binding. In contrast, resection of MtT resulted in tumor regression, a fall to normal of serum prolactin, and a nearly 3-fold increase in prolactin binding. Scatchard plots of prolactin binding data yield an apparent affinity constant, Ka, of 1.2 X 109 liters/mole for both tumors. The 4-fold-higher prolactin binding in the ovariectomy responsive variant suggests a positive correlation between ovariectomy response and the number of membrane prolactin-binding sites. No correlation between prolactin sensitivity and prolacting binding is apparent.

Animals

Effect of ovariectomy and ovariectomy with ovarian autotransplantation on feedlot performance and carcass characteristics of heifers.

Feedlot growth performance and carcass characteristics were examined in 96 crossbred heifers of continental breeding. Heifers were assigned to four treatment groups: intact control, sham ovariectomized, ovariectomized, and ovarian autografted. Ovarian autografted heifers were bilaterally ovariectomized via a left flank incision and one ovary was bisected sagittally and implanted in the musculature of the flank. Animals were fed a diet based on corn silage and were slaughtered at a weight of about 450 kg. There was no effect of treatment on feedlot performance or objectively measured carcass traits. However, carcasses of ovariectomized and ovarian autografted heifers had lower maturity scores than carcasses of the intact and sham-ovariectomy heifers. Blood samples were collected monthly throughout the study. Progesterone concentrations in these samples indicated that approximately 20% of the ovarian autografted heifers exhibited ovarian cyclicity. Examination of the transplanted ovaries at slaughter indicated that approximately 20% of the transplanted ovaries were resorbed. Cavitated, fluid-filled, thick-walled structures that were considered to be luteinized follicles were the most prominent structures found on the transplanted ovary; these were found in one-third of the ovarian autografted heifers. These results indicate that an ovary transplanted to the musculature can remain viable; however, its physiological function is disrupted and it does not affect rate or efficiency of gain or carcass composition compared to ovariectomized heifers.

Animals

Acute effects of ovariectomy and sham ovariectomy on pituitary-ovarian phenomena in the mouse.

Four- and 5-day cyclic mice housed with and without males, respectively, were autopsied at 10 a.m. on proestrus (P) or estrus (E) after no treatment, or after ovariectomy (Ovax) or sham Ovax at 10 a.m. or 4 p.m. on one of the preceding 3 days. Results indicate the ovarian must be in situ between 4 p.m. the day before P and 10 a.m. the day of P for a normal proestrous uterine weight increase to occur in both 4- and 5-day cyclic mice. For estrous cornification to occur, ovaries must be in situ between 10 a.m. and 4 p.m. on diestrus (D) in 4-day cyclic mice, and between 4 p.m. on D-I and 10 a.m. on D-II in 5-day cyclic mice. Sham Ovax tended to inhibit ovulation in both 4- and 5-day cyclic mice. The effects of both Ovax and sham Ovax on proestrous and estrous pituitary LH values were variable. ttiming of the feedback relationship between ovary and hypothalamus-pituitary in mice may be imprecise, leading to easy disruption of the estrous cycle in this species.

Animals

The influence of ovariectomy on luteinizing hormone concentrations in anestrous and cyclic sows.

In an effort to determine whether anestrus in swine is due to aberrant ovarian feedback control of gonadotropin release, this study contrasted the influence of ovariectomy on LH concentrations in serum of anestrous sows and in sows that returned to estrus following weaning. Blood samples were collected at 6-h intervals from 7 d prior to until 4 d after ovariectomy of 22 anestrous and 24 cyclic sows. Blood samples also were collected at 15-min intervals for 8 h at 2 d prior to and 2 d after ovariectomy. Sampling at 6-h intervals continued until 12 d after ovariectomy and additional 8-h windows of 15-min samples were taken at 7 and 12 d after ovariectomy of seven anestrous and nine diestrous sows. Mean LH concentrations and LH pulse frequencies were greater (P less than .05) 2 d after ovariectomy than 2 d prior to ovariectomy in both anestrous and diestrous sows. Mean pulse amplitude had increased by 2 d after ovariectomy in anestrous sows but did not change in cyclic sows. Baselines as determined from the mean of all LH measurements excluding pulses, remained the same in both anestrous and diestrous sows at 2 d after ovariectomy. Pulse frequency, pulse amplitude, and mean LH concentration were greater (P less than .05) in both anestrous and diestrous sows at 7 and 12 d after ovariectomy than at 2 d prior to and 2 d after ovariectomy. Pulse amplitude on d 7 and 12 after ovariectomy decreased (P less than .05) in both anestrous and diestrous sows relative to those observed at earlier times.(ABSTRACT TRUNCATED AT 250 WORDS)

Anestrus

Variable effect of unilateral or bilateral ovariectomy performed in young or adult animals on tissue plasminogen activator activity, plasminogen activator inhibition and plasmin inhibition.

Unilateral or bilateral ovariectomy was performed in young and adult rats. Mainly bilateral ovariectomy induced variable changes of plasminogen activator activity (PAA), plasminogen activator inhibition (PAI) and plasmin inhibition (PI) in key organs (brain, lungs, heart, aorta and kidneys). The most remarkable changes were induced after bilateral ovariectomy performed in young animals and mostly after two and three months of ovariectomy. Therefore, the effect of ovariectomy on tissue PAA, PAI or PI was variable and dependent on the extent of the ovariectomy (unilateral or bilateral), the age of the animal at ovariectomy (young or adult), the time after ovariectomy, and the organ. An additional interesting finding was the dissociation in the response of tissue anti-t-PA and anti-u-PA activities to ovariectomy in some of the organs studied.

Animals

Effect of ovariectomy and prednisolone on bone mineral content in rats: evaluation by single photon absorptiometry and radiogrammetry.

The effects of ovariectomy and prednisolone were studied for 9 months in 3-month-old rats on a moderately low calcium diet. Measurements were made by single photon absorptiometry of the femur at cortical and trabecular bone sites. Radiogrammetry was performed at the midshaft of the femur. During growth, body weight, bone size, and bone mineral content (BMC) increased in male rats more than in females. After ovariectomy, body weight increase was more pronounced, but bone mineral increase was lower than in controls. At the distal end of the femur, bone mineral density decreased after 3 months, and at the midshaft of the femur, medullary width increased significantly from 6 months on. Prednisolone in a dose of 0.5 mg/kg/day did not influence BMC. However, prednisolone treatment after ovariectomy induced a more pronounced effect on bone than ovariectomy alone. BMC increase was lower than in ovariectomy, and bone mineral density decreased significantly, especially at the distal end of the femur. After correction for differences in body weight, globally the same results were found. We conclude that (1) the combination of single photon absorptiometry and radiogrammetry allows the evaluation of growth and the effect of ovariectomy and prednisolone treatment in rats; (2) ovariectomy results in bone loss first at the distal end and later in the midshaft of the femur; (3) prednisolone in a dose of 0.5 mg/kg/day alone did not affect bone mass; and (4) prednisolone profoundly enhanced the effects of ovariectomy.

Absorptiometry, Photon

Changes in pulsatile LH secretion after ovariectomy in Ile-de-France ewes in two seasons.

Two experiments were conducted in Ile-de-France ewes to study changes in pulsatile LH secretion in ewes ovariectomized during anoestrus or during the midluteal phase of the oestrous cycle. In Exp. 1, blood samples were taken every 20 min for 12 h the day before ovariectomy (Day 0). After ovariectomy, samples were taken every 10 min for 6 h (10 ewes per group), on Days 1, 3, 7 and 15. In Exp. 2 samples were taken every 10 min for 6 h (10 ewes per group) on Days 7, 15, 30, 60, 90, 120, 150 and 180 after ovariectomy. Further samples were taken (5 ewes per group) at 9 and 12 months after ovariectomy. There were significant interactions between season and day of sampling for the interval between LH pulses in both experiments. LH pulse frequency increased within 1 day of ovariectomy and the increase was more rapid during the breeding season. There were clear seasonal differences in pulse frequency in Exp. 2. Compared with ewes ovariectomized in anoestrus, pulse frequency was significantly higher for ewes ovariectomized in the breeding season, from Day 7 until Day 120. Once pulse frequency had increased in ewes about the time of the normal breeding season, pulse frequency remained high and subsequent seasonal changes were greatly reduced. Pulse amplitude increased immediately after ovariectomy to reach a maximum on Day 7 and there were no differences between season of ovariectomy in the initial changes in amplitude. In Exp. 2, changes in amplitude followed changes in pulse interval and there was a significant interaction between season and day of sampling. There were no significant effects of season on nadir LH concentrations which increased throughout the duration of the experiments. These results show that, in ovariectomized ewes, LH pulse frequency observed on a given day depends on time after ovariectomy, season at the time of sampling and on previous exposure of ewes to stimulatory effects of season. The direct effects of season on LH pulse frequency and seasonal changes in sensitivity to steroid feedback may contribute to control of the breeding season and their relative contributions to the beginning and end of the breeding season may differ.

Animals

Long-term ovariectomy and hormone-induced sexual behavior, progestin receptors, and hypothalamic morphology in female rats.

Long-term ovariectomy reduces the ability of estradiol and progesterone treatment to induce sexual receptivity in female rats. Previous researchers suggested that this effect may be due to a decreased induction of neural progestin receptors by estradiol in the long-term ovariectomized rats. The present study was designed to replicate and extend this finding, and to search for neuroanatomical correlates by measuring the volume of the ventromedial nucleus (VMN) of the hypothalamus, a putative site of action of estradiol and progesterone for the induction of female sexual behavior. Long-term ovariectomy (5 to 6 weeks) as compared to short-term ovariectomy (1 week) reduced the ability of estradiol-17 beta and progesterone treatment to induce sexually receptive and proceptive behaviors. Consistent with previous reports, our data show that the reduced levels of cytosol progestin receptors after long-term ovariectomy and estradiol treatment are related to a reduced ability of estradiol to induce the receptors. Long-term ovariectomy did not affect the concentration of cytosol progestin receptors in the preoptic area, suggesting a neuroanatomical specificity to this effect. Contrary to our predictions, long-term ovariectomy did not affect the volume of the VMN. In fact, estradiol treatment, while blocking the effect of long-term ovariectomy on sexual behavior, decreased the volume of the VMN. Therefore, the measurement of the volume of the VMN is not a good predictor of the responsiveness to steroid hormone induction of sexual behavior.

Animals

Effect of early ovariectomy and steroid hormone replacement of embryo transport, development and implantation in mice.

Bilateral ovariectomy on Day 1 of pregnancy increased abnormal embryo numbers on Day 4 and delayed passage of embryos to the uterus. Progestins given on Day 1 reversed these effects; given on Day 3 they reduced numbers of abnormal embryos, but did not restore normal transport. Oestrogen given alone after ovariectomy increased embryo loss, but restored preimplantation embryo development to normal when given on Day 3 after progestins on Day 1. The results suggested that both oestrogen and progesterone were necessary for normal preimplantation embryo development in vivo. However, although Day-1 progestins produced the greatest improvement in embryo transport and preimplantation development, they supported only low implantation rates compared with progestins starting on Day 3, and no progestin treatment returned implantation rates to normal. Sham ovariectomy on Day 1 also reduced implantation rate, suggesting that surgical stress of Day-1 ovariectomy had major adverse effects on embryo viability. This view was supported by experiments involving unilateral ovariectomy, which produced abnormalities in embryo transport, development and implantation, but only on the operated side. Furthermore, the major abnormality induced in embryo development by unilateral and bilateral ovariectomy, viz embryonic autolysis, was not increased in experiments in which pregnancy was blocked by non-surgical antagonism of progesterone. It is concluded that abnormalities in embryo development induced by early ovariectomy are not caused by a deficit of endogenous hormones, but result largely from effects of surgical trauma on oviduct function which can be reversed by treatment with exogenous hormones.

Animals

The effects on the rat uterus and placenta of ovariectomy at day 10 of pregnancy.

A study was made of the changes in morphology and in nuclear incorporation of tritiated thymidine in the rat uterus and placenta after ovariectomy at day 10 of gestation. There was some individual variation between different animals in the results of the ovariectomy, but in general the effects on both maternal and fetal tissues were more severe than those reported to follow ovariectomy at later stages of pregnancy. Even in the animals where there was extensive placental survival 2 or 3 days after the ovariectomy, normal differentiation of the placental labyrinth did not occur and the fetuses failed to survive. Ovariectomy had a pronounced effect on the proliferative activity of uterine epithelial cells. The high labelling index in the control animals up to day 12 was markedly reduced in the ovariectomized animals; after day 13, however, the labelling index of the controls was reduced to a level lower than that of the ovariectomized animals. Nuclear labelling occurred in the glandular epithelium from two days after ovariectomy, but was never present in the controls. There was a marked reduction in the percentage of labelled nuclei in the uterine muscle and in the metrial gland after ovariectomy. In the metrial gland this was associated with a reduction in the number of typical granulated cells and with the appearance of numerous small round cells. It is suggested that the latter represented metrial gland cell precursors which had undergone impairment of their normal differentiation process.

Animals

The effects of ovariectomy and 17 beta-estradiol on cortical bone histomorphometry in growing rats.

The effects of ovariectomy for four weeks and of 17 beta-estradiol for three weeks on histomorphometry of the tibial diaphysis were determined in young rats. The effects of ovariectomy on histomorphometry of subcutaneous implants of demineralized bone matrix were also examined. Groups of young female rats were either ovariectomized or sham operated. After surgery, the animals were weight matched and pair fed. Despite the same caloric intake, ovariectomized rats grew more rapidly than pair-fed, sham-operated controls but were significantly heavier at sacrifice in only one of three experiments. Ovariectomy did not change mean serum calcium, phosphate, 25-hydroxyvitamin D (25-OHD), or 1,25-dihydroxyvitamin D [1,25(OH)2D] but significantly lowered mean serum magnesium. Serum estradiol was not detectable in ovariectomized animals. 17 beta-Estradiol in ovariectomized animals significantly increased mean serum estradiol and lowered mean serum phosphate but did not change mean serum calcium, magnesium, 25-OHD, or 1,25(OH)2D, as compared to values in sham-operated controls. Bone formation rate was significantly enhanced in ovariectomized animals at both the endosteal and periosteal surfaces of the tibial diaphysis as compared to values in sham-operated controls. The increase in bone formation rate was reversed by 17 beta-estradiol at the periosteal but not endosteal surface. Ovariectomy increased the bone apposition rate, mineralization rate, and osteoid thickness of the tibial diaphysis. These increases were reversed by 17 beta-estradiol. In implants, ovariectomy increased the resorption of implant matrix and enhanced the formation of new matrix. Ovariectomy resulted in increases in forming surface and resorbing surface in the implants.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Short- and long-term effects of ovariectomy on food intake, body weight, carcass composition, and brown adipose tissue in rats.

This experiment examined both the short-term and the long-term effects of ovariectomy on brown adipose tissue growth and function in rats to determine if reduced brown adipose tissue thermogenesis might contribute to the weight gain and adiposity. Brown adipose tissue function was assessed by measuring sympathetic nervous system activity (estimated by the rate of norepinephrine turnover) and mitochondrial proton conductance (estimated by specific GDP binding) in interscapular brown adipose tissue. Rats (n = 12 per group) were killed 0 (sham), 1, 2, 4, and 12 weeks after ovariectomy. During the first five weeks after ovariectomy rats overrate and rapidly gained weight. The weight gain was due to increases in all carcass components. Five weeks after ovariectomy food intake returned to control levels, and body weights stabilized 12-16% above sham-operated control weights for the duration of the experiment. Between week 4 and week 12 after surgery there was a redistribution of carcass composition, with decreases in carcass water and fat-free dry weights offset by a further increase in total carcass lipid. Brown adipose tissue pads were heavier in the 1-, 2-, and 4-week ovariectomy groups, but only in the 4-week group was the increase statistically significant. Brown adipose tissue protein, DNA, and norepinephrine content was unchanged 1-, 2-, 4-, or 12-weeks after ovariectomy. There was no difference in either the rate of norepinephrine turnover or specific mitochondrial GDP binding between sham-operated and 1-, 2-, 4-, or 12-week ovariectomized rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue, Brown