The effect of estradiol on the cell kinetics in the uterine and cervical epithelium of neonatal mice.

The effect of estradiol-17beta on the length of the various phases of the cell cycle was studied in the neonatal mouse uterine, and cervical epithelium. A double labelling method was used, and in addition labelled mitoses were counted. In the uterus proper, estradiol shortens the length of the total cell cycle. TC, from 17-9 hr to 15-7 hr, and the duration of S phase, Ts from 6-7 to 5-1 hr 6 hr after estradiol treatment. 12 hr after estradiol treatment, TC is shortened to 7-4 hr and Ts to 4-5 hr. The shortening of TC at 12 hr is manily due to an effect on TG1, which is shortened from 8-55 hr in untreated animals to 1-8 hr in estradiol treated animals. The TC of cervix epithelium cells in untreated animals was found to be 21-8 hr. After treating the mice for 6 hr with estradiol the tc was now increased to 47 hr and further to 61-2 hr following 12 hr treatment with the hormone. Ts increases from 8-3 hr to 15-2 hr following 6 hr estradiol treatment, and to 15-4 hr after 12 hr treatment. The effect is most pronounced in TG1, which is lengthened from 10-95 hr in untreated animals to 28-1 hr and 43 hr, respectively, in animals treated for either 6 or 12 hr with estradiol.     

Antifertility effects of neem (Azadirachta indica) oil by single intrauterine administration: a novel method for contraception

A novel use of neem (Azadirachta indica) oil, a traditional plant product, for long-term and reversible blocking of fertility after a single intrauterine application is described. Female Wistar rats of proven fertility were given a single dose (100 microliters) of neem oil by intrauterine route; control animals received the same volume of peanut oil. Whereas all control animals became pregnant and delivered normal litters, the rats treated with neem oil remained infertile for variable periods ranging from 107 to 180 days even after repeated matings with males of proven fertility. The block in fertility was, however, reversible as half of the animals regained fertility and delivered normal litters by five months after treatment, without any apparent teratogenic effects. Unilateral administration of neem oil in the uterus blocked pregnancy only on the side of application whereas the contralateral uterine horn treated with peanut oil had normally developing foetuses; no sign of implantation or foetal resorption was noted in the neem-oil-treated horn. The ovaries on both sides had 4-6 corpora lutea indicating no effect of treatment on ovarian functions. The animals treated with neem oil showed a significant leukocytic infiltration in the uterine epithelium between days 3 and 5 post coitum, i.e. during the pre-implantation period. Intrauterine application of neem oil appears to induce a pre-implantation block in fertility; the possible mechanisms of the antifertility action are discussed.     

THE EFFECT OF ESTRADIOL ON THE CELL KINETICS IN THE UTERINE AND CERVICAL EPITHELIUM OF NEONATAL MICE

The effect of estradiol-17β on the length of the various phases of the cell cycle was studied in the neonatal mouse uterine, and cervical epithelium. A double labelling method was used, and in addition labelled mitoses were counted. In the uterus proper, estradiol shortens the length of the total cell cycle, T_c, from 17-9 hr to 15-7 hr, and the duration of S phase, T_s, from 6–7 to 5-1 hr 6 hr after estradiol treatment. 12 hr after estradiol treatment, T_c is shortened to 7-4 hr and T_s to 4–5 hr. The shortening of T_c at 12 hr is mainly due to an effect on T_G1, which is shortened from 8–55 hr in untreated animals to 1–8 hr in estradiol treated animals. The T_c of cervix epithelium cells in untreated animals was found to be 21-8 hr. After treating the mice for 6 hr with estradiol the T_c was now increased to 47 hr and further to 61 -2 hr following 12 hr treatment with the hormone. T_s increases from 8-3 hr to 15-2 hr following 6 hr estradiol treatment, and to 15-4 hr after 12 hr treatment. The effect is most pronounced in T_G1, which is lengthened from 10–95 hr in untreated animals to 28-1 hr and 43 hr, respectively, in animals treated for either 6 or 12 hr with estradiol.     

Effects of hormone implants on estrus and ovulation in feral mares

Five groups of 30 captive feral mares each were implanted with silastic rods containing estradiol (E) and/or progesterone (P): E only with 8 g, P only with 24 g, P+HE with 8 g P + 8 g E, HP+E with 12 g P + 4 g E, HP+LE with 12 g P + 2 g E. Arbitrary group designations were differentiated by relative high (H) and low (L) amounts of steroid. Thirty mares received silastic rods containing no hormone (CI). Five mares from each group were bled every 2 wk for 4 mo and monthly for another 5 mo. All mares were tested for estrus by allowing them to stand in an alley between two pens of stallions and visually monitoring her response to the stallion. Serum P levels increased from 0.3 +/- 0.1 to 1.8 +/- 0.1 ng/ml in the P only group during the first 3 wk after implanting. Levels remained stable for the next 2 wk and then began a gradual decline. Serum P levels in the other groups were lower. Serum E levels were slightly increased in the groups receiving 8 g of E (E only and P+HE groups). Significantly fewer animals in the E only and P+HE groups exhibited estrus as compared with control animals (10 of 23 and 13 of 26 versus 22 of 25, respectively, P less than or equal to 0.003). However, animals receiving 24 g of P (P only) showed similar occurrences of estrus as controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

宫腔镜下宫腔粘连电切术后再粘连发生的因素调查分析

目的:调查与分析宫腔镜下宫腔粘连电切术后再粘连发生的因素,为预防术后再粘连的发生提供参考。方法:2016年2月到2018年11月选择在本院诊治的宫腔粘连患者112例,所有患者都给予宫腔镜下宫腔粘连电切术治疗,调查患者的一般资料,随访患者术后再粘连发生情况并进行多因素调查分析。结果:所有患者都顺利完成手术,围手术期无严重并发症发生;术后随访调查12个月,术后再粘连发生18例,发生率为16.1%。在112例患者中,不同病情、人流次数、宫腔操作次数、性生活年龄、产次患者的术后再粘连率对比差异都有统计学意义(P0.05)。多因素logistic回归方程结果显示病情、人流次数、宫腔操作次数、性生活年龄为影响患者术后再粘连发生的主要因素(P0.05)。结论:宫腔镜下宫腔粘连电切术后再粘连比较常见,其病情、人流次数、宫腔操作次数、性生活年龄为影响患者术后再粘连发生的主要危险因素。因此,术后提高女性的生活习惯和避孕意识,是防范宫腔粘再连的根本措施。     

Regulation of beta-endorphin and ACTH in brain by estradiol

The effect of estradiol on the brain concentration of immunoreactive beta-endorphin (beta-EP) and C-terminal ACTH (CLIP) was studied in ovariectomized rats. Dopamine, a known inhibitor of pituitary intermediate lobe pro-opiomelanocortin (POMC), was examined as a possible mediator of the estradiol induced changes in brain POMC. Animals were treated for 1 or 3 weeks with either 1) saline; 2) silastic estradiol implants; or 3) estradiol implants plus haloperidol 1 mg/kg/day. After one week of treatment no significant change in hypothalamic beta-EP content was noted in any group compared to the control level of 4.13 +/- .33 (SEM) pmoles although in the neurointermediate lobe beta-EP increased from 566 +/- 72 to 942 +/- 73 pmoles after haloperidol (p less than .005). After 3 weeks, however, hypothalamic beta-EP decreased from 3.96 +/- .28 to 2.74 +/- .19 pmoles (p less than .005) and C-terminal ACTH decreased from 3.78 +/- .33 to 2.82 +/- .18 pmoles (p less than .02) in the estradiol treated rats. This estradiol induced decrease in the hypothalamic content of beta-EP and C-terminal ACTH was not blocked by haloperidol. We conclude that estradiol lowers the hypothalamic content of beta-EP and CLIP and that this effect does not appear to be mediated by dopamine.     

Effect of progestins, estradiol, and coenzymes NAD and NADPH on the interconversion of estradiol and estrone in rabbit uterus in vitro

The biotransformation of estradiol (E2) and estrone (E1) in the uterus of rabbits treated with norgestrel (NG), norethindrone (NET), norethindrone acetate (NETA), progesterone (P4), and E2 either by subcutaneous injection in oil or by intrauterine steroid-releasing silastic implants was carried out under an in vitro short-term incubation system. The studies have shown that E2 stimulates 17 beta-hydroxysteroid dehydrogenase (17 beta-OHSD) much more than P4 as compared to untreated controls. The kinetic studies on E2 metabolism in the presence of added coenzyme NAD showed an initial rapid estrone formation and a gradual reconversion of E1 to E2. The addition of NADPH, ATP, and glucose-6-phosphate facilitates the reconversion of E1 to E2. The interconversion of E2 and estrone in the presence of coenzymes was five- to ten-fold higher in the endometrium than in the myometrium per milligram protein. Both E2 and progestins stimulate the uterine 17 beta-OHSD activity in rabbit uterus. This study further suggested that the hormone-induced metabolism of estradiol and estrone in the rabbit uterus is essentially modulated by the availability of coenzymes.     

Pregnancy in the domestic cat after vaginal or transcervical insemination with fresh and frozen semen

The objective was to compare pregnancy rates in domestic cats using fresh semen for intravaginal artificial insemination (IVI), either at the time of hCG treatment for induction of ovulation, or 28 h later, and to compare pregnancy rates following IVI or transcervical intrauterine insemination (IUI) of frozen-thawed semen. Eighteen queens were inseminated during 39 estrus cycles. Fresh semen with 13.5+/-5.4 x 10(6) sperm (range, 6.8-22 x 10(6)) collected by electroejaculation from four male cats was used in Experiment 1, and cryopreserved semen (20 x 10(6) sperm, with 70+/-5% post-thaw motility) from one male cat was used in Experiment 2. Serum concentrations of estradiol-17beta and progesterone were determined in most queens on the day of AI and again 30-40 days later. Treatment with 100 IU of hCG 3 days after the onset of estrus induced ovulation in 95% of treated queens. Pregnancy rates to IVI with fresh semen at the time of hCG administration versus 28 h later were not different (P=0.58); overall 33% (5/15) of the queens became pregnant. For frozen-thawed semen, AI was consistently done 28h after hCG administration; IUI and IVI resulted in pregnancy rates of 41.7% (5/12), whereas no queen (0/12) became pregnant by IVI (P=0.0083). In conclusion, an acceptable pregnancy rate was obtained with frozen-thawed semen in the domestic cat by non-surgical transcervical IUI; this method might also be useful in other small felids.     

Stimulation of 2',5'-oligoadenylate synthetase activity in sheep endometrium during pregnancy, by intrauterine infusion of ovine trophoblast protein-1, and by intramuscular administration of recombinant bovine interferon-alpha I1.

In Expt 1, activity of 2',5'-oligoadenylate (2',5'-A) synthetase in endometrium collected on Day 16 (oestrus is Day 0) from the uterine horn ipsilateral to the corpus luteum was greater (P less than 0.001) for pregnant (135.5 +/- 1.72 nmol/mg protein/h) than for cyclic ewes (58.5 +/- 0.99 nmol/mg protein/h). In pregnant ewes, activity of 2',5'-A synthetase in endometrium collected from the contralateral uterine horn (119.5 +/- 1.72 nmol/mg protein/h) did not differ from that of the ipsilateral horn. In Expt 2, three ovariectomized ewes were treated with progesterone for 10 days and then with oestrogen for 2 days. Activity of 2',5'-A synthetase on Day 13 was 18% greater (P less than 0.10) in endometrium collected from the uterine horn receiving infusions of 30 micrograms ovine trophoblast protein-1 (oTP-1) twice a day on Days 10, 11 and 12(57.7 +/- 0.22 nmol/mg protein/h) than from the uterine horn receiving control infusions of serum protein (SP; 48.8 +/- 0.22 nmol/mg protein/h). In Expt 3, activity of 2',5'-A synthetase on Day 15 was not significantly greater in endometrium collected from the uterine horn of cyclic ewes receiving infusions of 30 micrograms oTP-1 twice a day on Days 12, 13 and 14 (46.5 +/- 0.37 nmol/mg protein/h) than in endometrium from the uterine horn receiving infusions of SP (38.2 +/- 0.37 nmol/mg protein/h). When results of Expt 2 and Expt 3 were combined, intrauterine infusion of oTP-1 increased (P less than 0.05) activity of 2',5'-A synthetase in endometrium by 20%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dual effects of estradiol on normal and tumor pituitary cell multiplication

We have compared the effects of estradiol on the [3H]thymidine (TdR) incorporation into the DNA of 2 rat tissues whose growth is controlled by estradiol in vivo in 2 opposite directions: the normal anterior pituitary and the MtF4 pituitary tumor transplanted under the kidney capsule. Small pieces of pituitary or tumor from Fischer rats, treated or not by estradiol in silastic tubing, were incubated in vitro with [3H]TdR. The [3H]TdR incorporated per microgram DNA was decreased in tumor after 2 to 8 day-estradiol treatment while simultaneously, in the same rats, it was increased in the pituitary. In addition, we studied the effect of estradiol in vitro on the F4C1 cell line obtained from the MtF4 tumor. A dose-dependent decrease of both the [3H]TdR incorporated into DNA and the DNA amount was observed between 10(-6) and 10(-5) M estradiol. These results suggest that the control of the pituitary or MtF4 tumor growth by estradiol in vivo is in part due to an inhibition of cell multiplication. Although estradiol inhibits the growth of a clone of MtF4 tumor cells in vitro we cannot decide whether or not the in vivo effect of estradiol is direct.     

Effects of intrauterine foreign body on the localization of ( 3 H)-estradiol in rat uterine tissues, polymorphonuclear neutrophiles and eosinophiles

The effect of an intrauterine silk suture on localization of tritiated estradiol in the rat uterus was observed by dry autoradiography. 7 2.5 month old rats were ovariectomized and fitted with a 5-0 silk suture in one uterine horn. After 2 weeks, they were injected with 1 mcg estradiol 17-beta sc daily for 4 days, and 2 days later with .1 mcg per 100 gm body weight of 2,4,6,7-tritiated-estradiol-17-beta (specific activity 95 Ci per mM. Uteri from 6 rats were frozen-sectioned and mounted on dry emulsion-coated slides, at 10 and 60 minutes after sc injection, and 2 minutes after an iv injection in 1 rat. Autoradiograms observed 157 days later showed silver grains concentrated over nuclei in the outer layers of lumenal and glandular epithelium, substantia propria and muscularis in control horns. In uterine horns containing sutures, lesser radioactivity was observed in the basal epithelium and substantia propria, and higher activity in the nuclei of the stromal and glandular cells. No uptake was apparent in the eosinophiles or polymorphonuclear neutrophils which accumulated in the intrauterine suture horns.     

Effect of IUDs, Prostaglandins and Indomethacin on Decidual Cell Reaction in the Rat

The presence of an intrauterine device in the pseudopregnant (PSP) rat suppressed decidual cell reaction (DCR). Treatment with PGF_2α or PGE₂ also suppressed DCR, but had no effect on IUD horn. Treatment with PGF_2α from days 1–4 before trauma in ovariectomized rats treated with estradiol and progesterone did not have a significant effect on DCR. However, when PGF_2α was given for 4 days after trauma there was significant inhibition of DCR indicating a direct endometrial effect of PGF_2α. Inhibition of DCR was also recorded when indomethacin was administered to intact PSP or to ovariectomized rats maintained on estradiol and progesterone. This indicated that prostaglandins probably are necessary for normal DCR.     

有生育要求女性子宫内膜不典型增生的微创治疗

目的：探讨对于有生育要求的子宫内膜不典型增生患者采用宫腔镜微创治疗保留子宫的疗效。方法：回顾性分析新疆医科大学第一附属医院2000年1月-2013年3月因子宫内膜不典型增生行子宫内膜电切术（TCRE）的30例患者的临床资料。术后口服高效孕激素（甲羟孕酮）160mgqd3月或置入宫内左炔诺孕酮宫内缓释植入系统（曼月乐）,对两组患者月经及子宫内膜的病理进行随访。结果：两组患者TCRE手术均顺利完成,未发生严重并发症,术后月经过多、经期延长及贫血均得到明显改善,总有效率93．73％。其中口服高效孕激素组有效率为90．48％,置入曼月乐组有效率为96．30％。结论：对有随访条件的年轻的子宫内膜不典型增生患者,TCRE术联合孕激素或置入曼月乐是治疗的新选择,针对妇女的生育要求可以选择不同的术后用药。微创治疗提高了妇女的生存质量,并发症少。     

Changes in intrauterine pressure after oxytocin administration in reproductively normal mares and in those with a delay in uterine clearance

Intrauterine pressure was measured in 4 reproductively normal mares and 4 mares with delay in uterine clearance after administration of oxytocin to determine if intrauterine pressure varied between dosage and group. Changes in intrauterine pressure were measured during estrus, when a follicle was > or =35 mm, using a Millar "Mikro-tip" catheter that had 3 discrete pressure sensors/channels. Mares received 4 different treatments of 10, 5, 2.5 or 0 IU (vehicle) of oxytocin. The protocol for each treatment consisted of a 10-min baseline recording, administration of treatment and measurement of changes in intrauterine pressure for 65 min. After administration of the first two treatments, mares were rested for 2 h and the protocol repeated for the remaining 2 treatments. Changes in intrauterine pressure were measured on a physiograph and stored in a computer. The results were analyzed by 4x4 Latin Square Design analysis of variance (ANOVA) using the GLM procedure of the Statistical Analysis System. The ANOVA detected a main effect of treatment (P<0.01) and mare (nested within group; P<0.01) but no effect of channels, group or treatment-by-group interaction. There was a dose-dependent increase in uterine activity in both normal mares and those with delayed uterine clearance. A dose of 10 IU of oxytocin induced a larger number of uterine contractions (5.67+/-0.06) for a longer time (24.09+/-1.18 min) than the 5 IU (4.16+/-0.06 contractions and 16.31+/-1.18; P<0.01 min) or 2.5 IU dose (4.08+/-0.06 contractions and 17.61+/-1.18 min). The first intrauterine wave occurred most often near the tip of the horn in 10 of 12 recordings in normal mares and in 8 of 12 recordings in mares with delayed uterine clearance. It was then propagated from the middle of the horn to the uterine body just cranial to the cervix. There was no pattern of propagation for subsequent intrauterine pressure waves. We conclude that the difference in spontaneous clearance of the uterus between the 2 groups is not reflected in their response to exogenous oxytocin as determined by changes in intrauterine pressure.     

The effect of transcervical uterine manipulations on establishment of uterine infection in mares under the influence of progesterone

Four pony mares were used in a cross-over study to investigate the effect of different treatments on experimentally-induced endometritis. The mares were treated with progesterone to facilitate establishment of uterine infections. They received an intrauterine infusion of Streptococcus zooepidemicus 5 days after the start of progesterone therapy. Five days later, they were treated by intrauterine infusions of 2 g ampicillin in 50 ml sterile water or by sterile water without antibiotic for 3 consecutive days. Prior to infusion of Strep. zooepidemicus , no bacteria were cultured from the uteri of the mares. However, 5 days after infusion of Strep. zooepidemicus and prior to antibiotic therapy, mixed bacterial growths were cultured from endometrial swabbings. After antibiotic therapy, ampicillin-resistant organisms were cultured from endometrial swabbings. Two other progesterone-treated mares received an intrauterine infusion of sterile phosphate buffered saline instead of bacteria. Mixed bacterial cultures were recovered 5 days later from the endometrial swabbings of these mares. It was concluded that the high circulating concentrations of progesterone were probably responsible for the treatment failure and that in clinical situations, therapy involving transcervical manipulations should not be administered when mares are in diestrus.     

Temporal and spatial quantitation of nesting and mating behaviors among mice housed in a semi-natural environment

Enhanced behavioral complexity may be observed when animals are tested in naturalistic environments and engaging in nonforced social interactions. For each of six experimental runs, different groups of five adult Swiss-Webster mice (four ovariectomized females and a single male) were maintained under 12h dark:12h light in a 122 x 122 x 30.5-cm open box containing six peripheral "nestboxes." On Day 1, females were released into the box first and their nesting behavior was observed. Two days later, each female was injected with estradiol benzoate and the male was introduced into the environment. Females were injected with progesterone (P) 48 h later and the animals were observed for an additional 14 h. Behaviors were recorded with a video camera suspended over the apparatus. Mating occurred only post-P and males always mated preferentially with certain females. The amount of nesting behavior per female on Day 1 correlated significantly with the number of times each female was mated by the male (r = 0.57, P < 0.005). In all but one run, the male ejaculated with the female who performed the most nesting behavior. While 63% of mating was in the open, 56% of nestbox matings resulted in female postmating darting to alternate nestboxes; in 19% of these cases, the female quickly returned to the mating nestbox and was mated there again. Direct approaches by females to the male and behaviors which affect pacing were observed. These behaviors have not been reported previously for mice and may provide additional endpoints for the exploration of hormonal and genetic influences on reproductive behaviors.     

不同剂量戊酸雌二醇治疗宫腔粘连的临床效果

目的:观察不同剂量戊酸雌二醇治疗宫腔镜术后宫腔粘连的临床效果。方法:选取2013年6月-2015年3月在我院接受宫腔镜手术且术后出现宫腔粘连的患者80例,根据用药剂量不同,将所选患者分为小剂量组和大剂量组,每组40例。小剂量组患者给予戊酸雌二醇3 mg,大剂量组患者给予戊酸雌二醇9 mg治疗。观察并比较两组患者的临床疗效、月经恢复情况及不良反应发生率。结果:大剂量戊酸雌二醇治疗宫腔粘连的临床疗效显著优于小剂量组,差异具有统计学意义(P0.05)。大剂量戊酸雌二醇治疗宫腔粘连,患者术后的月经恢复率高于小剂量组,差异具有统计学意义(P0.05)。两组不良反应的发生率比较,差异无统计学意义(P0.05)。结论:9 mg戊酸雌二醇应用于宫腔镜术后具有较好的效果,能显著降低宫腔粘连发生率。     

Decreased cAMP responsiveness to glucagon in livers from ethynyl estradiol treated rats.

The effects of glucagon on the concentration and output of cAMP were studied in liver slices and in perfused livers from female rats and from animals treated with ethynyl estradiol (15 μg/kg daily for 14 days). The basal content of cAMP in liver slices, or of cAMP released into the perfusion medium in the absence of glucagon, was unaffected by prior treatment of the animal with estrogen. When glucagon was added to the medium, the concentration of cAMP in liver slices was 2.29 ± 0.32 and 1.10 ± 0.11 pmol cAMP/mg wet weight from control and ethynyl estradiol treated rats, respectively. When glucagon was added, the output of cAMP by perfused livers was maximal at 20 minutes with livers from either control or ethynyl estradiol treated rats. Output of cAMP by the perfused liver, when glucagon was added to the medium, was 8.76 ± 0.69 and 1.84 ± 0.08 nmol/g by livers from control and ethynyl estradiol treated rats, respectively. This effect was the same whether animals had been fasted for 12 hours previously, or were allowed free access to food until sacrifice. Clearly, as measured by cAMP accumulation, prior treatment of the rat with ethynyl estradiol reduced the sensitivity of the hepatic cAMP response to glucagon.     

Intrauterine movement of the early conceptus in barren and postpartum mares

The equine embryonic vesicle has been shown to be highly mobile prior to day 15, moving from one horn to the other many times per day. In Experiment 1, intrauterine mobility patterns of the vesicle were compared between barren and postpartum mares on days 12, 13, or 14, using an ultrasound instrument. Location of the vesicle (left horn, right horn, body) was determined every five minutes during six two-hour trials in each group. Averaged over all trials, the vesicle moved from one horn to the other 1.1 times per two-hour trial. There were no significant differences between barren and postpartum mares in the mean number of times the vesicle changed its location or in the amount of time the vesicle spent in the left versus right horn. In postpartum mares, the number of location changes and the time spent in a horn were not different between the formerly gravid horn and the nongravid horn. The reported frequent attachment of the vesicle to the formerly nongravid horn was not, therefore, attributable to a difference in the extent of mobility or the amount of time spent in the nongravid horn during the period of high intrauterine mobility. In Experiment 2, the rate of movement of the embryonic vesicle within the uterine body on days 12 through 14 was estimated to average 3.4 mm/min (range, 0-14 mm/min), based on fixed points of reference (cranial end of cervix, uterine cysts). Using time-lapse photography at one-minute intervals, a 14-day embryonic vesicle was monitored as it approached a cyst in the lumen of the uterine body. The vesicle encroached upon the cyst, forming an indentiation in the vesicle. It then moved over the top of the cyst to the other side and continued moving in the same direction.     

Sensitivity and specificity of bioassay of estrogenicity on mammary gland and uterus of female mice

Young intact (18 days of age) and adult ovariectomized (OV-X, ovariectomized between 21 to 24 days of age) C3H/Di mice were used to measure the estrogenicity on the basis of the growth response of mammary epithelial structures and weight of the uterus. The percentage area of the mammary fat pad occupied by mammary epithelial structures was progressively increased by 17beta estradiol from dose 0.001 microg.d(-1). The maximum effective dose of estradiol was 0.01 microg.d(-1) and the dose 10 microg.d(-1) of estradiol decreased mammary size to control levels (inverted-U-shaped dose-response curve). Progesterone alone progressively stimulated mammary growth in young intact females from dose 125 microg.d(-1), in adult OV-X animals from dose 1000 microg.d(-1). Both in young intact and adult OV-X animals, uterine weight progressively increased during estradiol treatment. Progesterone alone had no effect on uterine weight in young intact animals; in adult OV-X animals, uterine weight was increased starting from dose 250 microg.d(-1). Progesterone acted synergistically with estradiol to produce higher mammary growth than that in females treated with estradiol alone. The effects of a combination of estradiol plus progesterone in the mammary gland were mimicked by norethindrone acetate and inhibited by cortisol in both young intact and adult OV-X animals. Testosterone inhibited estradiol plus progesterone stimulated growth of mammary gland only in OV-X animals, but stimulated uterine weights in both young intact and adult OV-X animals. Spleen weight and size of mammary lymph nodes were not affected by estradiol, progesterone, norethindrone acetate or testosterone, but were decreased by cortisol. Cortisol also decreased the percent area of the mammary fat pad occupied by mammary epithelial structures, but had no effect on weight of the uterus. These results show that bioassay of estrogenicity in females is not specific. Mammary and uterine growth is stimulated not only by estrogens but also by progesterone and testosterone, respectively.