Effect of estrogen (E2) and progesterone (P4) on uterine antibacterial activity and immunoglobulin concentrations in mares was studied. In 2 in vitro experiments, 6 mixed-breed mares were ovariectomized, and uterine fluid and blood serum were analyzed. Antibacterial assay methods were used to determine inhibitory effects on Streptococcus zooepidemicus of uterine fluid samples collected on days 3, 5, and 8, and serum obtained on day 8 of treatment. Single radial immunodiffusion methods were used to quantify amounts of IgA and IgG in uterine fluid and serum on days 3, 5, 8, and 14 of treatment. Neither E2 nor P4 increased activity of serum and uterine fluid against S zooepidemicus. Numbers of colony-forming units per milliliter of bacteria were significantly (P < 0.01) lower in control Hanks' balanced salt solution with 1.0% gelatin (HBSSG) than in uterine fluids. Bacterial numbers were significantly (50%) greater in uterine fluids and serum than in HBSSG controls for both treatments. Both fluids, especially serum, supported significantly (P < 0.01) more growth of S zooepidemicus than did HBSSG when incubated for 0, 2, and 4 hours. These findings are in contrast to previous reports of antibacterial activity in the uterus of sexually intact mares undergoing an estrous cycle: great reduction of bacterial count in uterine fluid from mares in diestrus, and significant increases in bacterial numbers in uterine fluid or serum from mares in estrus. Treatment comparisons between serum and uterine fluid IgA and IgG concentrations were not significantly different, although overall IgA concentration in the uterus was higher than concentration in serum. The IgG concentration in uterine fluid was higher in P4- than E2-treated mares. However, IgG concentration was significantly (P < 0.01) higher in uterine fluid on day 8 in P4-treated mares than on day 3 or 5. Results of this study indicate that neither immunoglobulin concentration nor hormone treatment has a direct effect on streptocidal activity.

The mechanism of estrogen-induced myelotoxicosis is unknown, although evidence indicates that estrogen does not directly damage the bone marrow granulocyte-macrophage progenitor cells and that the thymus is a probable mediator of the bone marrow suppression. Estrogen-induced production of a myelopoiesis-inhibitory factor by canine thymic stromal cells in vitro has been observed. Then, presence of a myelopoiesis-inhibitory factor in canine serum was investigated immediately after estrogen administration in vivo. Maximal reduction in colony-forming units-granulocyte/macrophage growth by sera from individual dogs varied. Individual dog sensitivity to estrogen-induced myelotoxicosis is seen clinically, and the cause is unknown. This serum factor could have a role in the eventual bone marrow hypoplasia seen in estrogen-treated dogs and is possibly the same factor produced by cultured thymic stromal cells exposed to estrogen.

The influence of cortisol on estrogen synthesis by the bovine placenta and the importance of the delta 4 and delta 5 pathway for estrogen production were investigated. For experiment 1, portions of fetal villi (200 mg) were incubated for 48 hours with 0, 10, 100, and 1,000 ng of cortisol/ml with [3H]androstenedione (3H-A) or [3H]pregnenolone (3H-P5). Villi were also incubated for 4, 28, and 52 hours with or without cortisol (500 ng/ml) and with 3H-A or 3H-P5 (experiment 2). The conversion of various [3H]steroid metabolites such as A, P5, 17 alpha-OH-pregnenolone (17 alpha-OH-P5), progesterone (P4), 17 alpha-OH-P4, cholesterol (chol), and chol plus lipoprotein (500 micrograms/ml) into estrogen was measured during a 4-hour incubation (experiment 3). In experiment 1, cortisol increased conversion of 3H-A and 3H-P5 into estrogen by 3 to 41% and 7 to 34%, respectively, in a dose-dependent manner (P < 0.05). In experiment 2, times of incubation did not influence conversion of 3H-A into estrogen, which, however, was increased significantly (P < 0.05) over all times of incubation by administration of 500 ng of cortisol/ml. Conversion of 3H-P5 into estrogen increased over time of incubation and was stimulated by cortisol (P < 0.05). However, there was no interaction between cortisol treatment and time of incubation. In experiment 3, conversion of 3H-A, 3H-P5, and 3H-17 alpha-OH-P5 into estrogen was greater than the conversion of the other precursors tested. Mean conversion of 3H-A, 3H-P5, 3H-17 alpha-OH-P5, 3H-P, 3H-17 alpha-OH-P4, 3H-chol, and 3H-chol plus lipoprotein was 23%, 10.6%, 11.0%, 1.8%, 1.8%, 0.3% and 0.7%, respectively. Our results suggest that, in cows, the delta 5 pathway is the preferred pathway for placental estrogen synthesis and that cortisol directly stimulates estrogen production, probably by activating enzymes involved in this pathway.

Objective--To evaluate the effects of diethylstilbestrol (DES) or alpha-zearalanol (zeranol) on fetal development, gestation duration, and number of offspring. Design-Study effects of prenatal administration of DES or zeranol on various pre- and perinatal variables in an experimental group of mice, compared with effects in a control group. Animal--Pregnant NMRI mice. Procedure--Diethylstilbestrol or zeranol (150 mg/kg of body weight) or vehicle (controls) was administered sc to pregnant mice on days 9 and 10 of gestation. Fetuses from pregnant mice of each group were counted and weighed, and their size and head length were recorded. Additional pregnant mice delivered their fetuses naturally, and pups from each group were counted and their sex was determined. At the end of gestation, abortions were evaluated. All data were statistically analyzed. Results--Mean number of fetuses was significantly lower (P < 0.0001) in DES-treated (4.59 +/- 0.48) than in control mice (8.33 +/- 0.49). Both estrogenic substances significantly reduced fetal size and weight (P < 0.0001), compared with control mice. Diethylstilbestrol significantly increased abortion frequency (P < 0.0001) and gestation duration (P < 0.0001), compared with values for control mice. A reduced number of live pups (P < 0.0001) from pregnant mice administered DES (5.48 +/- 0.38) or zeranol (5.97 +/- 0.49) was observed, compared with control mice (8.52 +/- 0.50), because of reduced number of male offspring (P < 0.0001). Conclusions--Diethylstilbestrol or zeranol administered during mid-pregnancy leads to decreased fetal weight and size and lower numbers of male offspring at birth. Likewise, DES induced a significant increase in abortions and gestation duration.

Forty-four female American Shorthair cats with inflammatory uterine disease or infertility were evaluated. Data collected included age, month of diagnosis, housing, reproductive history, results of bacteriologic culture of uterine specimens, serum concentrations of estrogen, progesterone, and prolactin and histopathologic features of the ovaries and uterus. Histologically, the ovaries of 19 cats were dominated by active or cystic follicles, whereas 25 cats had luteal-phase ovaries. Of the 25 cats with active corpora lutea, 20 had either recently weaned litters (n = 11) without subsequent exposure to a male cat, or had been housed individually for lengthy periods (n = 9). The finding of active corpora lutea under these circumstances indicates that in queens, ovulation may occur by mechanisms not involving coitus. Prominent, active corpora lutea on the ovaries were associated with adenomatotic proliferative changes in the superficial and glandular epithelium of the uterus and with myometrial hyperplasia, compared with the uterus of cats with follicular ovaries (P < 0.01). Serum progesterone concentration greater than or equal to 1.87 ng/ml was consistently associated with luteal-phase ovaries. Serum progesterone values less than or equal to 0.15 ng/ml were consistently associated with follicular-phase ovaries. Escherichia coli was the organism most commonly isolated from uterine contents.

Objective--To determine the relative role of endogenous prostaglandin F2 alpha (PGF2 alpha) secretion in cloprostenol-induced abortion in mares that no longer require luteal progesterone secretion for maintenance of pregnancy, and to evaluate the ability of a prostaglandin cyclooxygenase inhibitor (flunixin meglumine) to prevent cloprostenol-induced abortion. Design--The effect of flunixin meglumine on PGF2 alpha secretion and outcome of pregnancy was compared between mares treated with cloprostenol only and mares treated with cloprostenol plus flunixin meglumine. Animals--Five pregnant mares, aged 4 to 15 years, of light-horse type. Procedure--Cloprostenol (250 micrograms) was administered at 24-hour intervals to 5 pregnant mares. Flunixin meglumine (500 mg, IV) was administered at 8-hour intervals starting 15 minutes before the first cloprostenol administration. Hourly blood samples were analyzed for 15-ketodihydro-PGF2 alpha, progesterone, and estrogen concentrations. Previously reported data on cloprostenol-induced abortion in 6 pregnant mares treated daily with cloprostenol only were used as historic controls. Results--The mean (+/- SEM) interval from first cloprostenol administration to fetal expulsion 56.4 (+/- 13.7) hours and number of cloprostenol administrations 3.2 (+/- 0.6) in the 5 flunixin meglumine-treated mares were not significantly different, compared with values for 6 pregnant mares treated daily with cloprostenol only, 48.6 (+/- 5.6) hours and 2.8 (+/- 0.2) cloprostenol administrations. Flunixin meglumine did not inhibit endogenous PGF2 alpha secretion. Prostaglandin F2 alpha secretion rates on the day before and day of fetal expulsion were similar in both groups. Conclusion--Flunixin meglumine at a dosage of 500 mg/animal, administered IV every 8 hours, is ineffective in modulating uterine PGF2 alpha secretion during cloprostenol-induced abortion. Clinical Relevance--Flunixin meglumine is ineffective in the modulation of prostaglandin-induced uterine PGF2 alpha secretion and, therefore, does not offer a viable alternative for the prevention of abortion in mares at risk of abortion because of systemic illness.

The effects of subcutaneous administration of a commercially available estradiol 17 beta implant on hematologic values and the chemiluminescence response of neutrophils were evaluated in 14 steers. Chemiluminescence and hematologic values were measured in treated (n = 8) and nontreated (n = 6) steers on days -14, -7, and -1 prior to implantation. Estradiol 17 beta was implanted into the treated group of steers on day 0, and blood samples were obtained from all steers on days 1, 2, 3, 4, 8, 15, 22, 29, 36, 43, and 50. The concentration of estrogen in serum was significantly (P = 0.0120) higher following implantation. Chemiluminescence and hematologic indices were not significantly affected by either implant status or serum concentrations of estrogen. The results of this study suggested that the use of implants containing estradiol 17 beta for promotion of weight gain in steers will not result in alterations of hematologic values or the neutrophil respiratory burst.

Cytosolic assay was used to detect gonadal steroid receptors in brain tumor tissue from 6 dogs and 2 cats. For 4 samples, the maximal number of binding sites and the equilibrium dissociation constant were calculated, using Scatchard analysis. The concentration of receptor protein that was discovered was similar to that detected in hormone-sensitive tumors.

Ten tumors from 7 dogs were analyzed for estrogen receptors. Of 9 determined to be mast cell tumors, 6 were determined not to have estrogen receptors (less than 3 fmol of estradiol/mg of cytosol protein) and 3 were questionable (3 to 10 fmol of estradiol/mg). One tumor was a mixed mammary tumor and was determined to have estrogen receptors (12 fmol of estradiol/mg). Histologic grading of the mast cell tumors did not suggest a correlation with estrogen receptor values.