Delayed anovulatory syndrome induced by estradiol in female C57BL/6J mice: age-like neuroendocrine, but not ovarian, impairments

These studies describe induction of a delayed anovulatory syndrome (DAS) by estradiol (E2) in female C57BL/6J mice. Six days after birth, female mice were injected s.c. with 0.1 micrograms estradiol benzoate or oil. Over 90% of the oil-injected controls exhibited estrous cycles from 2 to 9 mo of age. In contrast, 60% of the E2-injected mice exhibited estrous cycles at 2 mo of age but were acyclic by 9 mo; these mice were considered to have exhibited a DAS, and had longer cycles than controls. At 12 mo, ovarian impairments were assessed by examining 1) ovulation after s.c. injection of 5 IU human chorionic gonadotropin (hCG), and 2) estrous cycles after grafting into young (3-mo-old) hosts. Simultaneously, neuroendocrine impairments were assessed by examining 1) the surge of luteinizing hormone (LH) induced by E2 implants after ovariectomy, and 2) estrous cycles after receiving ovarian grafts from 3-mo-old mice. Ovaries from DAS and control mice ovulated equally in response to hCG. Ovaries from DAS mice grafted into young ovariectomized hosts supported 30% more cycles, of shorter period, compared with ovaries from control donors. However, the E2-induced LH surge was 50% smaller in DAS mice than in controls. Ovariectomized DAS hosts with ovarian grafts from young mice supported 70% fewer estrous cycles, of longer period, compared with ovariectomized control hosts with young grafts. We conclude that the E2-induced DAS in female mice is not due to ovarian impairments, but seems to result from neuroendocrine impairments.     

Effect of decidual tissue on the uterine production of prostaglandins in pseudopregnant rats.

The concentration of prostaglandin F (PGF) in uterine vein plasma of non-traumatized pseudopregnant rats and pseudopregnant rats with deciduomata were not significantly different from each other at any of the times of pseudopregnancy studied (Days 7, 10 and 12). There was a significant increase in PGF levels on Day 10 in both groups of pseudopregnant animals (P less than 0-05) compared to the Day 4 values, and PGE values were significantly greater on Day 10 in the decidual tissue-bearing rats (P less than 0-01). A slight but not significant elevation in PGE concentration was observed on Days 7 and 12 in rats with deciduomata, but there was no significant difference in the control rats on Days 4, 7, 10 or 12. The results indicate that the prolongation of pseudopregnancy in rats with deciduomata is not due to a decreased production of uterine PGs and lend support to the recent suggestion of a luteotrophic effect of decidual tissue in the rat.     

Long-term effects of ovariectomy on osteoporosis and obesity in estrogen-receptor-β-deleted mice

Untreated BERKO mice demonstrate few abnormalities in bone phenotype and recent ovariectomy has few effects on various bone characteristics in these mice. Long-term studies on the bone phenotype of intact and ovariectomized mice are unavailable. Using quantitative computed tomography (qCT), we determined various parameters of the metaphysis of the tibia in sham-ovariectomized (intact) and ovariectomized BERKO and wildtype mice. Body weight and estrogen-regulated fat were also measured. Mice underwent surgery (ovariectomy or sham) at 3 mo of age, and qCT analysis was performed every 2 to 4 mo until mice were 12 mo old. Ovariectomized wildtype mice gained body weight and their fat depot increased in size within 2 mo after ovariectomy. Obesity developed later in ovariectomized BERKO mice, which became significantly heavier than their wildtype counterparts. Ovariectomized wildtype mice lost trabecular density more rapidly than did ovariectomized BERKO mice, which did not show similar loss in trabecular density until at least 7 mo after ovariectomy. At the latest studied time point (9 mo after surgery), cortical area was significantly larger in ovariectomized BERKO mice than ovariectomized wildtype mice. The absence of ERβ in ovariectomized BERKO mice during the first 3 to 5 mo after ovariectomy had protective effects against obesity and trabecular rarification; this protective effect disappeared at later time points.     

Influences of pre- and postnatal testosterone treatment on defeminization of sexual receptivity in pigs

Sexual receptivity was evaluated in female and male pigs that had experienced varying periods of exposure to testosterone pre- and postnatally. For prenatal exposure, pregnant sows were treated with testosterone propionate (TP) from Day 29-35 or Day 39-45 of gestation at a dosage that caused virilization of the external genitalia of their female offspring. Eighty-three percent of the females that received TP prenatally had regular estrous cycles, but reached puberty later than control females. Only 26% of the females that received TP both pre- and postnatally (4-6 mo of age) were observed in estrus by 10 mo of age. After ovariectomy and acute treatment with estradiol benzoate (EB), the proportion of females that showed the immobilization response (receptivity) was similar for all groups of females independent of pre- or postnatal TP treatment. Females treated prenatally from Day 39-45 showed the immobilization response for fewer days after treatment with a high dosage of EB than did controls. On the basis of these observations, we conclude that receptivity in female pigs is not affected greatly by testosterone treatment at the stages of development that were investigated. Males castrated at birth and treated with a single injection of EB after 9.5 mo showed the immobilization response. In contrast, few males castrated at 8 mo or castrated at birth and treated with TP from 3 to 6 mo showed the immobilization response after EB treatment. These observations provide direct evidence for a postnatal component of testosterone-dependent defeminization of receptivity in male pigs.     

Effect of follicular fluid treatment on follicle-stimulating hormone, luteinizing hormone and compensatory ovarian hypertrophy in prepuberal gilts

Prepuberal 130-day-old gilts were treated with 10 ml of charcoal-stripped porcine serum (PS), whole porcine follicular fluid (WpFF) or charcoal-stripped pFF (CpFF) twice daily beginning the day before and continuing 8 days after unilateral ovariectomy (ULO). Follicle-stimulating hormone (FSH) declined for the first 14 h after ULO in WpFF and CpFF gilts and then by 24 h returned to values observed at or before ULO, whereas FSH was increased nearly twofold at 14 h in PS gilts. At 8 days after ULO the remaining ovaries from PS-treated gilts were heavier than ovaries from follicular fluid-treated gilts. In a second experiment, ovariectomized 130-day-old gilts were assigned to either a group infused with PS, a group infused with 5 ml CpFF, or a group infused with 10 ml Cpff at 18 and 2 h before a gonadotropin-releasing hormone (GnRH) challenge. Porcine follicular fluid had no effect on luteinizing hormone (LH) response to GnRH, depressed the FSH response to a 10-micrograms challenge of GnRH, but had no effect on FSH response to a 50-micrograms challenge of GnRH. In a third study, gilts were subjected to sham ovariectomy (Sham) or ULO at 130 days of age. GnRH (10 micrograms) was given on Days 1, 2 or 8 after surgery. The response to GnRH in ULO versus Sham gilts did not differ for FSH or LH on any day.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of egg development and implantation in rats after post-coital administration of the progesterone antagonist RU 486

RU 486 was administered to rats on Day 1 or Days 1 + 2 of pregnancy. Endometrial sensitivity (i.e. decidualization in response to oil instillation) was delayed by 2.5 mg/kg injected s.c. on Day 1, and almost half of the animals also exhibited a delay in implantation of 1-2 days. Higher doses (5 or 10 mg/kg) administered on Days 1 + 2 reduced the number of implantations to zero in all animals. Apparently normal morulae were found up to the evening of Day 4 in the oviduct and/or the uterus of most animals. However, on the morning of Day 5, ova were detected in only 25% of the animals and all were in the uterus: none was at the blastocyst stage and they appeared to be degenerated or compacted morulae. Egg survival and rate of egg recovery from the uterus was not improved by early ovariectomy, showing that this antiprogestagen acts on these events independently of the presence of circulating oestrogens.     

Bone resorption and prostaglandin production by mouse calvaria in vitro: response to exogenous prostaglandins and their precursor fatty acids

Mouse calvaria were maintained in organ culture for 96 h and endogenous prostaglandin production and active bone resorption (45Ca release) measured. After a lag phase of 12 h, active resorption increased over the 96 h period. The amounts of prostaglandins released into the culture medium (measured by radioimmunoassay) were highest in the first 24 h of culture. Unless these were removed by preculturing for 24 h, or suppressed by indomethacin, no response to exogenous PGE2, or prostaglandin precursors could be demonstrated. Bone resorption was stimulated after preculture by both PGE2 and PGF2 alpha in a dose-dependent manner (10-8M-10-5M), with PGE2 being the more potent. Collagen synthesis was unaffected by PGF2 alpha, whereas PGE2 (10-5M) had an inhibitory effect. Eicosatrienoic acid did not stimulate bone resorption at lower concentrations (10-7M-1-5M), but was inhibitory at 10-4M. Arachidonic acid also inhibited resorption at 10-4m, but at lower concentrations (10-7M-10-5M) increased active resorption. This was concomitant with a rise in PGE2 and PGF2 alpha levels, PGE2 production being significantly higher than PGF2 alpha. The effects of PGE2 (10-8M) and PGF2 alpha (10-8M) appeared additive; there was no evidence of synergistic or antagonistic effects when varying ratios of PGE2: PGF2 alpha were employed.     

Chronic elevation of estradiol in young ovariectomized rats causes aging-like loss of steroid-induced luteinizing hormone surges

This study was designed to test the hypothesis that the loss of LH surges in response to the stimulatory actions of estradiol and progesterone in middle-aged, persistent-estrous (PE) rats may be caused by chronic elevations in circulating estradiol. Five groups of regularly cycling young rats received an s.c. estradiol implant immediately after ovariectomy (Day 0). For determination of LH surges, blood samples were collected hourly between 1200-1900 h from each of the five groups at one of the following times: 3 days, or 1, 2, 4, or 8 wk later. On the next day, either progesterone (0.5 mg/100 g BW) or corn oil was injected s.c. at 1200 h, and samples were obtained as before. Incidence and amplitude of estradiol-induced LH surges decreased during the first 2 wk of estradiol treatment, after which no surges occurred. Progesterone enhanced the incidence and amplitude of estradiol-induced LH surges thus delaying their disappearance. These results support our hypothesis and demonstrate that the stimulatory actions of estradiol and progesterone on the LH surge sequentially diminish with time after exposure to estradiol in young rats. Thus, young rats chronically treated with estradiol may be a useful model for studying the mechanisms whereby LH surges are abolished in middle age during the hyperestrogenic state of PE.     

Promoting effect of ovariectomy on hepatocellular tumorigenesis induced in mice by 3'-methyl-4-dimethylaminoazobenzene.

The treatment of female C57BL/6 x DS-F1 mice with 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) at 10, 12, 14, 16 and 18 days of age resulted in the development of hepatocellular adenomatous nodules after 10 months of age. Ovariectomy in these mice at 1 month of age hastened the development of adenomatous nodules, which then first appeared at 8 months of age. The incidence of adenomatous nodules in females ovariectomized at the age of 1 month was much higher than that in intact females of the same age. These results showed that the ovaries exerted a suppressive effect on the development of adenomatous nodules. To determine the time from which the ovaries exert this suppressive effect, females were ovariectomized at 4, 6, 8, and 10 months of age, and the incidences of adenomatous nodules were compared at 10 and 12 months of age. Delayed ovariectomy after 8 months of age did decrease the incidence of adenomatous nodules at 10 and 12 months of age, but ovariectomy after 4 and 6 months of age did not. When the incidence of adenomatous nodules in females ovariectomized at 10 months of age was examined over the subsequent 6 months, it became significantly higher after 14 months of age compared with that in intact females. The results show that the ovariectomy has the promoting effect on the development of adenomatous nodules in the liver induced by 3'-Me-DAB after 6 months of age.     

Effects of pleural pressure and abdominal pressure on diaphragmatic blood flow

Alveolar transfer of prostaglandin E2 (PGE2) was characterized in isolated perfused guinea pig lungs (n = 19) by measuring radioactivity appearing in the venous effluent during 30 min after intratracheal instillation of [3H]PGE2, [14C]-mannitol, and [125I]iodoantipyrine. Recovery of lipid-soluble [125I]iodoantipyrine [91 +/- 3% (SE)] after 30 min was used to estimate total 3H and 14C delivered to the exchanging region of lung at time 0. In seven control lungs, 58 +/- 4% of [14C]mannitol and 16 +/- 4% of [3H]PGE2 was retained 10 min after instillation. Neither perfusion with diphloretin phosphate (10 micrograms/ml; n = 4) nor hypothermia (5 degrees C; n = 5) significantly affected the amount of [14C]mannitol retained; however, [3H]PGE2 remaining in these lungs increased significantly to 36 +/- 4 and 53 +/- 2%, respectively. Addition of unlabeled PGE2 (200 micrograms) to the instilled solution (n = 3) increased retention of both [14C]mannitol (80 +/- 3%) and [3H]PGE2 (65 +/- 4%). Alveolar transfer of [3H]PGE2 was calculated as the difference in percent retention of [14C]mannitol and [3H]PGE2 and normalized to that of [14C]mannitol. After 10 min, alveolar transfer of [3H]PGE2 was 71 +/- 8% in control lungs but was decreased to 26 +/- 7, 10 +/- 5, and 19 +/- 6% by diphloretin phosphate, hypothermia, or unlabeled PGE2, respectively. These data suggest that alveolar clearance of PGE2 involves a saturable drug- and temperature-sensitive process.     

Reduced gonadotropin release in response to progesterone or gonadotropin releasing hormone (GnRH) in old female rats

Ovariectomized rats that were 3–4, 12 or 22 months old were injected s.c. with 4 mg, of testosterone propionate and 3 days later were injected s.c. with 2.8 mg. progesterone or the oil vehicle. Blood samples were collected by heart puncture 5 hrs. later. Serum levels of LH and FSH decreased significantly as age increased. Progesterone significantly increased serum LH and FSH levels regardless of age. The increase in serum LH concentration attributed to progesterone was greatest in the young and least in the old rats. To determine if age effects were due to differences in pituitary response to GnRH, ovariectomized rats that were 2.5 to 23 months old were injected i.v. with GnRH at doses of 100 ng or 40 ng/100 g body weight or were primed with 25 mg progesterone and 50 μg estradiol-benzoate 3 days before an injection of 2 ng GnRH/100 g body weight. Blood was obtained by heart puncture before and 20 min. after GnRH. In each experiment serum LH levels significantly decreased with increasing age but were significantly elevated by GnRH. This increase in serum LH level in response to GnRH declined with increasing age. The data suggest that the elevation in serum LH level in response to GnRH declines as a result of aging in female rats and that this effect is independent of circulating ovarian steroid levels.     

Effect of indomethacin and prostaglandin E2 on structural differentiation of rat endometrium during artificially induced decidualization

Morphological differentiation of uterine stromal and luminal epithelial cells was studied in steroid-injected ovariectomized rats following unilateral intrauterine instillation of sesame oil, phosphate-buffered saline containing gelatin (PBSG), PBSG + indomethacin (IM; an inhibitor of prostaglandin synthesis), or PBSG + IM + prostaglandin E2 (PGE2). The latter two treatments were preceded by a subcutaneous injection of IM. Uteri were examined by light and electron microscopy at intervals between 8 and 120 hr (n = 4/treatment/time). Differentiation began in the periluminal antimesometrial region and progressed peripherally and towards the mesometrial aspect in all groups. Structural features and timing of differentiation were similar for oil-injected and PBSG-infused uteri. Administration of IM inhibited the onset of the decidual cell reaction and had deleterious effects on the luminal epithelium. Inclusion of PGE2 in the instillate accelerated stromal cell differentiation and overcame the inhibitory effect of IM. The results implicate prostaglandins, particularly PGE2, in endometrial transformation during decidualization.     

Age-related alterations in pulsatile luteinizing hormone release: effects of long-term ovariectomy, repeated pregnancies and naloxone

Aging of the female reproductive system may be regulated by changes at the hypothalamic, pituitary, and ovarian levels. Long-term ovariectomy (LT-OVX) and/or multiple pregnancies delay age-related deterioration of several parameters of reproductive potential in rodents. We tested whether long-term suppression of cyclic ovarian hormone release that is normally associated with the 4- to 5-day estrous cycle decelerates age-related decreases in the frequency of luteinizing hormone (LH) pulses to assess whether hormonal milieu influences the rate of aging of the pulse generator. We determined the percentage of rats exhibiting pulsatile LH secretion, mean LH levels, and amplitude and frequency of LH pulses in seven groups of ovariectomized (OVX) rats. Young (3-4 mo), middle-aged (8-10 mo), and old (18-22 mo) virgin rats, ovariectomized 4 wk (4WK-OVX) prior to experimentation, were used to determine the effect of age. The effect of long-term ovarian hormone deprivation was tested by ovariectomizing rats at 2-3 mo of age and using them when they were middle-aged (8-10 months) or old (18-22 mo). The effect of deprivation of cyclic increases in ovarian hormones associated with repeated estrous cycles was tested by using retired breeder (RB) rats that had been ovariectomized 4 wk prior to experimentation. Each rat was implanted with a right atrial cannula and bled the next day at 10-min intervals for 3 h.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intraluminally injected oil induces changes in vascular permeability in the 'sensitized' and 'non-sensitized' uterus of the mouse

After suitable sensitization of ovariectomized mice with progesterone and oestradiol, the intrauterine instillation of oil produces a massive decidual cell reaction. Vascular permeability, as reflected by the extra-vascular accumulation of 125I-labelled human serum albumin, increased after oil instillation and was maintained at 2-3 times control values for at least the next 3 days. Although oil instillation did not produce a decidual response in females treated with progesterone alone, an increase in vascular permeability (about 2 times control levels) still occurred. This response peaked 8 h after oil instillation and was not maintained. These results indicate that the progesterone-dominated uterus which has not been sensitized with oestradiol cannot be viewed as completely unresponsive to the stimulus of oil and demonstrate that a marked increase in vascular permeability is not itself sufficient to induce decidualization of progesterone-dominated uterine stromal cells. The uterine extravascular accumulation of 125I-labelled albumin was increased both in association with tribromoethanol anaesthesia and after oestradiol treatment of progesterone-primed animals. In pregnant mice, the appearance of Pontamine Sky Blue spots provided an earlier indication of implantation than did determination of total uterine extravascular 125I-labelled albumin accumulation.     

Prostaglandin E1 inhibits N-formyl-methionyl-leucyl-phenylalanine-mediated depolarization responses by decreasing the proportion of responsive cells without affecting chemotaxin-induced forward light scatter changes

Hypaque-Ficoll-purified human polymorphonuclear neutrophils (PMN) equilibrated with the membrane potential-sensitive probe 3,3'dipentyloxacarbocyanine [di-O-C(5)(3)] were incubated with buffer or cytochalasin B (cyto B) followed by incubation with prostaglandin E1 (PGE1) (0 to 10(-5) M) for 5 min at 37 degrees C. The cells were then stimulated with N-formyl-methionyl-leucyl-phenylalanine (FMLP) (0 to 10(-5) M). Changes in forward light scatter (FWD-SC), 90 degrees scatter (90 degrees -SC), and fluorescence intensity were measured by flow cytometry to determine the effects of PGE1 on FMLP-induced shape change, secretion, and membrane potential responses, respectively. In other experiments, the effects of PGE1 preincubation on FMLP +/- cyto B and phorbol myristate acetate-induced (O2) production were measured by superoxide dismutase-inhibitable cyto c reduction. PGE1 had no direct effects on the FWD-SC, 90 degrees-SC, or resting potential fluorescence of unstimulated or cyto B-pretreated PMN. PGE1 produced a dose-dependent inhibition of the proportion of depolarizing PMN in response to FMLP, which was maximal at 10(-6) M (42.1 +/- 6.9% inhibition, p less than 0.005), but was apparent at 10(-8) M. The PGE1-induced inhibition was maximal after 30 sec of incubation at 37 degrees C and was caused by a decrease in the maximal percentage of depolarizing PMN without a significant change in the FMLP dose-response curve (Km = 2.43 vs 3.62 X 10(-8) M, control vs PGE1-treated) or an inhibition in the degree of depolarization by the responding subpopulation. PGE1 also inhibited the loss of 90 degrees-SC induced by FMLP in cyto B-pretreated cells (secretion response) (46.2 +/- 16.5% inhibition of the maximal 90 degrees-SC loss, n = 5, p less than 0.005), but did not affect the increase in FWD-SC seen with FMLP-induced PMN activation or the ability of cyto B to recruit more PMN to depolarize. PGE1 also inhibited FMLP +/- cyto B-induced O2 production in a dose-dependent fashion; phorbol myristate acetate-induced O2 production was also slightly inhibited, but only at high PGE1 concentrations. The data indicate that PGE1 inhibits FMLP-induced cell activation by a mechanism that involves a step distal to the recruitment of unresponsive PMN by cyto B, and that PGE1 is capable of inhibiting depolarization responses without affecting FMLP-induced shape change, providing more support for a dissociation between the two activation pathways.     

Interaction between dietary intake and ovariectomy on concentrations of insulin-like growth factor-I, GH and LH in plasma of heifers

The objective of this study was to determine if alterations in dietary intake and(or) ovariectomy influence plasma concentrations of IGF-I, GH and LH in heifers. Cyclic heifers (n = 23) were individually fed for 10 wk either 1) 1.8% of body weight in dry matter per day (GAIN; n = 7) 2) 1.1% of body weight in dry matter per day (MAINT; n = 8); or 3) 0.7% of body weight in dry matter per day (LOSE; n = 8). After 10 wk of dietary treatment, heifers were ovariectomized 36 to 40 h following the second injection of prostaglandin F2alpha analog (2 injections 11 d apart). Heifers weighed 444 +/- 13, 387 +/- 8, and 349 +/- 9 kg in the GAIN, MAINT and LOSE groups, respectively, at the time of ovariectomy; the average daily weight gains during the 10-wk period were 0.96, 0.17 and -0.31 kg, respectively (P < 0.001), for the 3 groups. Blood plasma was collected for 6 h at 15-min intervals 1 d before and 2 wk after ovariectomy. The MAINT group of heifers had greater IGF-I concentrations than either the LOSE or GAIN groups; IGF-I decreased (P < 0.05) by 23 and 35% after ovariectomy in the MAINT and GAIN groups, respectively, but did not change (P > 0.10) in the LOSE groups. Dietary restriction tended to increase (P < 0.10) GH pulse frequency and mean GH. Ovariectomy had no effect (P > 0.10) on mean GH or GH pulse frequency but increased (P < 0.05) GH pulse amplitude in the GAIN groups. Dietary treatment had no effect (P > 0.10) on mean LH, or LH pulse amplitude and frequency. However, across dietary treatments, ovariectomy increased mean LH and LH pulse frequency but did not affect (P > 0.10) LH pulse amplitude. In summary, dietary restriction increased GH secretion while ovariectomy increased LH secretion. There appears to be a dichotomy of response between GH and IGF-I in the way heifers respond to dietary treatment and(or) ovariectomy.     

Interindividual variation in the responses of cultured human lymphocytes to exposure from DNA damaging chemical agents: interindividual variation to carcinogen exposure.

Human population variability to standardized doses of N-acetoxy-2-acetylaminofluorene (NA-AAF) and 7, 12-dimethylbenz(a) anthracene (DMBA) was determined in cultured lymphocytes by measuring (a) differential stimulation of unscheduled DNA synthesis after 1 h induction of DNA damage by 10 micrometer NA-AAF, (b) the level of NA-AAF induced chromosome aberrations remaining after 8 h of DNA-repair synthesis, and (c) the level of [3H]DMBA bound to DNA after 18 h incubation of resting lymphocytes in 5 micrometer DMBA. All 3 parameters indicated individual variation to carcinogen exposure and were correlated to the population differences in age, sex, blood pressure and mortality rates. Males always had a greater potential to accumulate DNA-damage than did females regardless of the sampled population. DNA-damage potentials increased with increasing age, blood pressure or mortality rates. There was always proportionally greater DNA-damage potentials in the males than in females. The in vitro response of mature granulocytes to a 10 micrometer NA-AAF dose, as estimated by [3H] thymidine incorporation from unscheduled DNA synthesis, was much lower than lymphocyte response. Nevertheless, individual variations in granulocyte NA-AAF induced unscheduled DNA synthesis paralleled the inter-individual fluctuations observed in the lymphocyte responses to NA-AAF.     

Decidualization in rats given 5alpha-dihydrotestosterone or its propionate neonatally.

In Experiment 1, female rats were given a single subcutaneous injection of 1.25 mg 5alpha-dihydrotestosterone (DHT) or its propionate (DHTP) on day 5 of postnatal life. All of them showed regular estrous cycles as adults like untreated control animals. At about 60 days of age, the rats were ovariectomized and given 7 daily injections of 2 mg progesterone (P) plus 0.2 mug estradiol-17beta (ED). Uterine trauma applied on the 4th day of P-ED injections resulted in well developed deciduomata in all animals by the day after the last injection. This made a sharp contrast to the failure of female rats receiving testosterone propionate (TP) neonatally to give a positive response under similar experimental conditions (Takewaki and Ohta, 1974). The mean weight of traumatized horns was significantly larger in DHTP-treated rats (but not in DHT-treated rats) than in controls. In Experiment 2, rats were ovariectomized on day 4 and given a dose of 1.25 mg DHT or DHTP on day 5. Controls were ovariectomized on day 4 but not given any steroid on the next day. A series of 7 daily injections of 2 mg P plus 0.2 mug ED was started at about 60 days of age, after the animals had received 3 daily injections of 0.2 mug ED or 30 daily injections of 0.1 mug ED. Incidence of deciduomata following uterine traumatization was markedly lowered only in animals treated with DHTP neonatally and given 0.1 mug ED for 30 days as adults, no significant differences being found in both incidence and size of deciduomata among the other groups. It was suggested that the effects of neonatal steroid administration on uterine responsiveness in adulthood are specific to the steroid. The previous conclusion that persistent estrus in androgen-sterilized rats plays a part in the reduction of uterine responsiveness was confirmed. An exposure of rats to estrogen for a prolonged postpuberal period was without effect, unless the animals had received enough androgen neonatally.     

Age-related changes in the suppression of serum luteinizing hormone by estradiol-17beta in developing steers

Serum luteinizing hormone (LH) concentrations were measured at 4, 6, 8 and 10 mo of age in estradiol-17beta (E(2))-treated (n = 4) and contemporary control steers (n = 4). Serum LH was measured in samples collected at 30-min intervals starting at 0600 h for 12 h and for an additional 6 h following luteinizing hormone-releasing hormone (LHRH) injection. Estradiol-17beta suppressed mean serum LH concentrations at all ages (P<0.01), but it suppressed pulsatile release of LH only at 4 and 6 mo (P<0.01), not 8 and 10 mo of age. Luteinizing hormone release in response to LHRH, expressed as the area under the secretory curve, was larger and LH concentrations returned to pre-LHRH levels later in E(2)-treated steers (P<0.01). Peak LH concentrations after LHRH varied with age (P<0.05) but not E(2) treatment. These results suggest that E(2) suppression of LH in steers occurs at the hypothalamic level and developmental changes take place within the hypothalamicpituitary axis in absence of androgen feedback from the testis.