Differential effects of progesterone on lactation and nursing behavior in late pregnant and postparturient rats

In the past, studies on the effects of progesterone injections before or after birth concentrated only on lactation or nursing behavior. The present study is a report of the effects of progesterone on both events, in the same strain of rat, across a number of groups, administered either during pregnancy or after birth. In the first part of the experiment, 2 mg doses of progesterone subcutaneously were injected into nulliparous Sprague-Dawley rats from Days 18–23 of gestation. The injections delayed the onset of birth, caused a high mortality among young, and produced young that failed to thrive. In spite of this, nursing behavior appeared normal. There were no significant differences in the latency or duration of crouching behavior between the progesterone and oil-injected control groups. Thus the difficulties appeared to be with lactation. Because mammary glands contained milk, problems with secretory activation in the glands were ruled out. Even though the pups suckled teats, they got no milk, suggesting dysfunctions in milk release. To determine whether progesterone might alter maternal behavior once it was established after birth, 2-mg doses of progesterone were injected during the first postpartal week. They were found to depress litter weights and increase the latency to crouch over pups. During the second postpartal week, the injections reduced the latency to crouch, causing females to act vigorously toward pups at a time when maternal behavior typically starts to decline. Thus, depending upon the stage of the reproductive cycle in which progesterone is introduced, it can either inhibit or enhance nursing behavior. Moreover, the action of progesterone during late gestation appears to be only on milk release.     

Sexual preference in female rats during estrous cycle, pregnancy and lactation.

Choice of a male or female social contact was studied in intact female rats in a runway-choice apparatus during estrous cycle, pregnancy, and lactation. The male was chosen significantly more often during proestrus/estrus than during the diestrous days of the cycle. During pregnancy this preference in choice declined only to reappear gradually during the lactation period. The shifts in the level of motivation to seek out the male support previous studies and point to the significance of estrogen in producing the preference for the male.     

Failure of protein synthesis inhibition to block progesterone desensitization of lordosis in female rats

Progesterone's desensitization effect on lordosis has been shown to correlate with a decreased concentration of hypothalamic progestin receptors after progesterone injection. In a recent study, one group of investigators found that the protein synthesis inhibitor anisomycin appeared to block progesterone's desensitization effect. Despite decreased levels of cytoplasmic progestin receptors, progesterone + anisomycin-treated rats exhibited a high level of lordosis four hr after a second progesterone injection. Because this finding conflicts with a progestin receptor model of progesterone's desensitization effect, we investigated it further. In the first experiments, ovariectomized rats were injected with estradiol benzoate followed 24 hr later by either progesterone or vehicle. Anisomycin injected 3 hr after progesterone, at a dose that causes inhibition of hypothalamic protein synthesis for at least 4 hr, was without effect on progesterone desensitization a day later. In other experiments silastic implants containing estradiol were inserted into ovariectomized rats. Forty-five hr later, rats received progesterone or vehicle, followed by injections of anisomycin or saline. Rats receiving anisomycin + progesterone were still highly receptive at 30 hr while saline + progesterone controls were not. Furthermore, the results were similar 4 hr after a second injection of progesterone at 30 hr. In a related experiment, we confirmed that anisomycin delayed dramatically termination of the period of sexual receptivity. In this laboratory anisomycin does not seem to block progesterone's desensitization effect. However, with certain procedures anisomycin delays the termination of sexual receptivity. Thus it is important in investigations of the mechanism of progesterone's desensitization effect that animals be tested prior to the second progesterone injection to determine if they are actually responding to the progesterone.     

Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.     

The effects of lactation and ambient temperature on the body temperature of female Norway rats

Norway rat dams were placed in an ambient temperature of 4°C, 22°C, or 28°C. Body temperatures were recorded over a two hour period on three days; each female was observed on Day 4 and Day 10 of lactation and three days after lactation was stopped. Body temperatures were initially higher during lactation than after lactation had stopped. Dams were less able to maintain their body temperatures in the 28°C ambience on Day 4 of lactation than after lactation, and on Day 10 of lactation, were even less able to maintain their body temperatures than on Day 4. During lactation, dams were able to maintain and even increase their body temperatures in the 4°C ambience. The data support the hypothesis that the acute hyperthermia encountered by rat dams during contact with their litters may be due to a physical restriction on maternal heat loss.     

Effects of neonatal exposure to progesterone on sexual behavior of male and female rats

Lactating females received daily injections of progesterone or oil, and their offspring were gonadectomized in adulthood and tested for both musculine and feminine sexual behavior elicited by estrogen, progesterone, and testosterone regimens. Male offspring of progesterone treated females exhibited significant impairment of masculine behavior elicited by both estrogen and testosterone. Latency and frequency of mounts and intromissions of those males which did engage in sexual behavior were not significantly different for the two groups. There were nonsignificant trends toward demasculinization of progesterone treated females and feminization of progesterone treated males. Progesterone administered to estrogen primed males failed to facilitate lordosis. There were no progesterone related differences in body weight at any time nor in testis or accessory organ weights of males. The results of this experiment confirm our previous finding of reduced sexual competence of intact male rats exposed neonatally to moderately increased levels of progesterone, and indicate that this effect is not the result of diminished adult hormone levels. Neonatal exposure to progesterone appears to have minimal or no effect on feminine sexual behavior of rats.     

Estradiol plus progesterone treatment and precopulatory behavior in ovariectomized female rats

The effects of progesterone in ovariectomized female Wistar rats, chronically injected with estradiol plus progesterone, were determined utilizing a scale of sexual responsiveness (SR) based on the hierarchical organization of copulatory (lordosis posture) and precopulatory (presenting posture, hopping, darting) behaviors. Standardized mating tests were performed 48 hours after estradiol dipropionate application (E) and 4 hours after progesterone (P) application. Experiment 1: Starting with the 5th day following ovariectomy animals in two groups were injected SC with 15 μg E in regular weekly intervals (for 8 weeks), the animals in one of the groups obtaining further SC injections of 1.0 mg P 44 hours later. The SR intensity induced by E and P application gradually increased and was eventually higher than in the E application. Experiment 2: Animals primed with 6 μg E were divided into four groups that received different P doses: 0.0, 0.4, 1.0 or 2.2 mg. This treatment lasted 11 weeks. Increased SR occurred only with the 1.0 and 2.2 mg P doses. However, these doses were equally effective. Experiment 3: Animals in five groups obtained 3, 5, 10, 15 or 30 μg E for 7 weeks. Every female was also given weekly injections of P that ranged from 0.0 to 2.4 mg. With 3, 5 and 10 μg E there were only small differences in the SR induced by small and large doses of P. On the other hand, animals receiving 15 μg E were differentially affected by P injections. Higher injected doses of P increased the SR induced by 15 μg E. The 30μg E dose combined with injections of P around 0.6 mg induced higher SR than when combined with injections of P over 1.0 mg. Experiment 4: Animals utilized in Experiment 3 which had received 30 μg E were subjected to further experimentation. The deletion of P caused a rapid decrease in SR. A predicted increase in SR was observed after reintroducing the 0.6 mg P administration. Finally, after the E and P administrations were stopped, precopulatory behavior disappeared but the females still exhibited the lordosis posture two weeks later. Based on these results the general conclusion is made that the dose-response relationship between progesterone and proceptive (precopulatory) behavior is dependent on the quantity of estradiol which is jointly administered. By certain combinations of dosage levels of estradiol and progesterone, the highest level of sexual responsiveness can be induced in ovariectomized rats.     

Potential risks of maternal administration of Mucophylline on the pups of albino rats during lactation

The present study was undertaken to evaluate the potential risks of the mucolytic and broncholytic drug, Theophylline derivatives (Mucophylline) maternally administered on the pups. The nursing rats orally administered from 1st postpartum day (PPD) to 21th PPD with two different doses 30.83 mg/kg (low dose) and 66.61 mg/kg (Human equivalent dose (HED)). On the 21th PPD, the postnatal developmental signs, skeletal malformation and the histopathology of neonatal liver, kidney and brain were examined. Our results showed that Mucophylline induced a significant reduction in the neonatal weight and length, delayed, weak and incomplete ossification, wavy ribs and the neonatal liver revealed histopathological changes, pyknotic hepatocytes, cytoplasmic vacuolization, dilated sinusoid and necrotic area. Kidney revealed alternation changes, enlargement of the glomerulus, renal tubules degeneration and lymphatic infiltration. Brain (cerebral cortex and cerebellum) showed neurodegenerative changes, vacuolization of neuropil, congested and dilated blood vessel and dark stain neurons. Our results showed that the activities of non-enzymatic (GSH) and enzymatic (GST, CAT) antioxidants were insignificantly decrease in both neonatal brain and liver tissues of rats administered with 30.83 mg/kg and 61.66 mg/kg of Mucophylline and insignificant increase in MDA levels in both neonatal brain and liver tissues. However, significant reduction (P ≤ 0.05) in the content of GR was recorded in neonatal brain tissue of rats administered with 30.83 mg/kg and 61.66 mg/kg of Mucophylline during lactation period in comparison with control. These support and proof the potential risks of the maternal administration of Mucophylline on pups.     

Variations in the cellular proliferation of prolactin cells from late pregnancy to lactation in rats

Lactation is a physiological process associated with hyperactivity of hypophyseal prolactin-producing cells. It is known that the percentage of these cells is increased during lactation, although there are discrepancies in the reports regarding the mechanisms responsible for increasing the number of prolactin cells. In order to analyse whether this increase is a result of previous proliferation, variations in the proliferation rate of prolactin-positive cells were determined from late pregnancy to lactation in adult female rats by means of observation of the immunohistochemical expression of PCNA as a marker of cellular proliferation. During late pregnancy, a very significant increase in the percentage of proliferating prolactin cells was observed in comparison to non-pregnant females in the proestrus phase (p < 0.01). Although the percentage of prolactin-positive cells after one week of lactation was higher than in non-lactating or in pregnant females (p < 0.01), the proliferation rate was lower than in the other groups studied. In sum, our results suggest that late pregnancy constitutes a preliminary proliferative phase preparatory to the ensuing lactation phase and that endocrine changes in late pregnancy involve the cellular proliferation of hypophyseal prolactin cells in order to prepare the gland for later demands and to prevent proliferative changes from occurring during lactation.     

Withdrawal effects from progesterone and estradiol relate to individual risk-taking and explorative behavior in female rats

Withdrawal from progesterone and estradiol has been used as an animal model of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). In the clinical population individual sensitivity to sex steroid hormones, personality and heredity influence PMS/PMDD. Understanding the phenotypic risk factors of PMS/PMDD and drug development requires an animal model which incorporates individual steroid sensitivity. The main objective of this study was to investigate whether the individual trait of risk-taking and exploration influence the severity of PEWD in female rats. Thirty-two female Wistar rats in their diestrus phase were tested in the open field (OF) and divided into high responders (HR) and low responders (LR). Injections were given i.p. twice daily for 6 days, either 5 mg/kg progesterone combined with 10 µg/kg 17β-estradiol, or vehicle (sesame oil). After a 24-hour withdrawal the animals were tested in the elevated plus maze (EPM). Blood samples for CORT analysis were collected after both behavioral tests. The HR rats withdrawn from progesterone and estradiol, spent less time on the EPM open arms and had lower CORT levels than the HR controls. The LR group showed no differences in EPM behavior and CORT levels during PEWD. The controls showed a stable trait of risk-taking and exploration, indicated by behavioral and CORT level correlations between the OF and EPM tests. These findings show that female rats with the trait of risk-taking and explorative behavior (HR) are more affected by PEWD.     

Food selection during recovery from protein restriction in lactation.

Lactating rats were fed a 12% or 25% casein diet. After the pups were weaned on Day 21, dams were given ad lib access to three food cups containing protein, carbohydrate, and fat. Both groups were hyperphagic for three to four weeks. Previously, protein-restricted rats consumed more protein than controls during Weeks 2 and 3, but protein intake returned to control levels as body weight recovered.     

Prostaglandin E2-induced lordosis in estrogen-primed female hamsters: relationship to progesterone action

Intraperitoneal injection of 10, 50, 100 or 250 μg of prostaglandin E₂ (PGE₂) resulted in a dose-dependent facilitation of lordosis in ovariectomized female hamsters given estradiol-17β in silastic capsules 72 hr earlier. The ability of progesterone to facilitate lordosis in the absence of PGE₂ mediation was investigated by injecting ovariectomized, estrogen-primed females with indomethacin, a prostaglandin synthesis inhibitor, at 1.5 hr before and after progesterone administration. Conversely, the ability of PGE₂ to facilitate receptivity independently of progesterone mediation was examined by injecting 100 μg or 250 μg PGE₂ to estrogen-primed, ovariectomized-adrenalectomized females. Because indomethacin did not interfere with progesterone-induced lordosis, and because PGE₂-induced lordosis was not abolished by adrenalectomy, it was concluded that induction of lordosis by progesterone and PGE₂ are mutually independent processes. A final study investigated the ability of PGE₂ to facilitate lordosis during the period of progesterone-induced inhibition of receptivity. When compared to PGE₂-treated controls, the administration of 200 μg progesterone 24 hr prior to 100 μg PGE₂ injection significantly reduced the proportion of ovariectomized estrogen-primed females who exhibited lordosis. These results are consistent with the view that progesterone inhibits lordosis via some general mechanism such as interference with the estrogen priming process.     

孕激素受体在雌性山羊颈胸神经节的表达

目的观察雌性山羊颈胸神经节内神经元是否具备接受孕激素作用的条件。方法采用免疫组织化学SP法观察孕激素受体(PR)在成年雌性山羊颈胸神经节的表达。结果雌性山羊颈胸神经节内神经元胞体均呈孕激素受体免疫反应阳性;卫星细胞、施万细胞、神经突起和神经纤维中也有较弱的着色。神经元的细胞膜和细胞质呈棕褐色为强阳性,而神经元的细胞核着色出现异质性:85.10%的神经元细胞核为强阳性,其中31.91%的核仁呈清亮的空泡,为阴性;而14.90%的神经元细胞核呈空泡状不着色,其中7.45%的核仁为强阳性。卫星细胞、施万细胞和神经纤维均呈淡黄色,为弱阳性。图像分析表明,神经元胞体PR的相对表达量与其他非神经成分相比差异性极显著(P0.01)。结论在颈胸神经节内神经元是孕激素作用的主要靶细胞之一,提示孕激素有可能通过影响雌性山羊颈胸神经节内神经元的活动参与心脏功能的神经调节,而颈胸神经节上的PR可能作为一个网络节点协调孕激素对心脏功能的内分泌调节和自主神经对心脏活动的神经调节。     

Attractivity of male rats induced by estradiol and progesterone

From the present study it appears that castrated male rats can be made attractive to intact males by estradiol benzoate plus progesterone (EB + P). For the determination of attractivity a residential plus-maze was used in which the resident male could choose between the company of the experimental male and that of an ovariectomized female with or without EB + P. In one experiment the males were castrated in adulthood; these animals were less attractive than the ovariectomized females with a similar hormone treatment. In a second experiment it was found that males that had been castrated at birth were as attractive as the ovariectomized females, after treatment with EB + P. These findings indicate that the attractivity that can be induced by EP + P in gonadectomized adult rats is somewhat but not wholly reduced if androgen is present during the neonatal period.     

Perinatal progesterone and learning,social and reproductive behavior in rats

Progesterone was administered to rats perinatally via either maternal Silastic implants (Experiment 1) or daily maternal injections (Experiment 2). Animals were tested at 14 days of age on an active avoidance task (Experiments 1 and 2), and in adulthood on a Lashley III maze task, active and passive avoidance tasks, and open field activity (Experiment 1) and on social and reproductive behavior measures (Experiment 2). Adult males' performance on the Lashley III task was significantly impaired by progesterone treatment in Experiment 1 as were male copulatory and aggressive behaviors in Experiment 2. Perinatal progesterone as administered in these experiments does not results in an animal model for the reported enhancement of human performance consequent to prenatal progesterone treatment. It is, however, consistent with an interpretation of demasculinization of behavior patterns.     

Stress related effects in the control of sexual receptivity and in the secretion of progesterone by the adrenals in cyclic female rats

The present study examined the acute effects of ether anaesthesia and/or blood removal by heart puncture on progesterone blood concentration at different times of proestrus and on subsequent estrous mating behavior during the night following proestrus in sham adrenalectomized and adrenalectomized 4-day cyclic female rats. A statistically significant increase in blood progesterone concentration was observed on proestrus at 09:00, 13:30 and 15:30, a very short time after heart puncture under a 3 min ether anaesthesia in sham adrenalectomized rats as compared to their adrenalectomized counterparts. Following this blood removal procedure at the preceding times a greater number of sham adrenalectomized female rats displayed mating behavior (17/20) than their adrenalectomized counterparts (11/23). It is suggested that adrenocortical related effects of ether anaesthesia and/or surgical manipulations may be involved in the display of estrous sexual receptivity in the rat.     

Modultion of the Golgi apparatus in stimulated and nonstimulated prolactin cells of female rats

The three-dimensional structure of the Golgi apparatus and its compartments in prolactin cells has been examined in lactating rats in which secretion of prolactin was suppressed by removing the litter or stimulated by allowing the pups to suckle again. As soon as 2 hr after removal of the litter, large irregular progranules and numerous large pale vesicles accumulated in the trans-Golgi area together with vesicular or tubular fragments. The cis-tubular network was no longer recognizable on the cis-face of the Golgi ribbon; the saccules of the midcompartment were partitined by narrow fissures and also became perforated in register by numerous fenestrations of various sizes and irregular contours. The concomitant appearance of numerous vesicles in the cavities thus formed as well as in the surrounding cytoplasm indicated that they probably arose by the progressive cavitation and fragmentation of saccules of the mid compartment. Such a process, which reached a maximum between 4 and 6 hr after removal of the litter from the mother, was no longer observed at 8 and 12 hr, at which time intervals the Golgi apparatus was reduced in size with no cis-tubular elements and progranules on its trans-aspect and few vesicles in its surroundings. When mothers, separated from their litters for a period of 12 hr, were returned to their pups for 20 min, the cis-tubular network reappeared on the cis-aspect of the Golgi stacks and presumably formed by fusion of vesicles and anastomosed tubules located next to the cisternae of the rough endoplasmic reticulum. In addition, the structure of the midsaccules returned to the stimulated condition, and early progranules were again segregated within the trans-most saccules of the Golgi stack. Hence, the Golgi apparatus of prolactin cells was rapidly and deeply modified in the presence or absence of stimulation. © 1993 Wiley-Liss, Inc.     

Behavioral effects of ethynyl estrogens in the female rat

The synthetic analogues of estradiol, ethynyl estradiol and mestranol, are used in oral contraceptives. Their effects on food intake and sexual behavior were evaluated in female rats, and compared with those of estradiol. It was found (Experiment 1) that both ethynyl estradiol and mestranol reduced food intake reliably, and more than estradiol. Water intake and body weight followed similar trends. Ethynyl estradiol, but not mestranol, plus progesterone stimulated proceptive and receptive behavior in ovariectomized female rats. Daily administration of ethynyl estrogens without progesterone showed similar trends (Experiment 3). It is hoped that these studies provide guidelines for further work on the effects of synthetic estrogens on sub-primate and primate behavior.