Hormonal and behavioral aspects of maternal care in the hamster: a review.

This review covers a description of the maternal behavior cycle in the hamster and relationships between the endocrine system and prepartum changes in activity, aggression, sexual receptivity, and maternal care. Postpartum maternal behavior consists of the mother's "normal" cannibalism of some portion of her litter, the formation of a bond between mother and her young, the development of behavioral synchrony between the mother and her pups, and maternal aggression toward conspecifics. The maternal responses of virgin female, male, and juvenile animals are described and methodological considerations in the testing of both virgin and parturient animals are presented. Finally, a theoretical framework for considering the regulation of maternal care in the hamster is presented. Two main phases of regulation are proposed; an onset phase that that originates prepartum and depends on the physiological conditions of pregnancy and a maintenance phase which provides for the continuation of maternal care during lactation and is based on both endogenous maternal factors and external litter-related stimuli. A transition period beginning at parturition facilitates the shift between the onset and maintenance phases.

The effects of phenobarbital and gonadal steroids on periovulatory serum levels of luteinizing hormone and follicle-stimulating hormone in the hamster.

The occurrence of ovulation and serum levels of LH and FSH (measured by radioimmunoassay) were determined in periovulatory hamsters injected with an ovulation-blocking dose of phenobarbital (Phen) combined with progesterone (P), estradiol-17beta (E2), or testosterone (T). Proestrous hamsters were treated at 1300 h with Phen plus oil, P, P plus E2, E2, T, or a second injection of Phen at 2000 h. Each treatment group was divided into 3 subgroups, each of which was serially bled 4 times at 6 h intervals beginning at 1200, 1400, and 1600 h on proestrus. Phen blocked ovulation on the next morning in all animals, while treatments that included P (1 mg) restored the normal complement of ova in 65-75% of the animals. Neither E2 (1, 10 or 50 mug) nor T (0.1 or 1 mg) overcame the Phen block of ovulation. Control hamsters had peak levels of LH between 1400 and 1800 h and a biphasic release of FSH consisting of a peak at 1600 h on proestrus, a return to basal levels at 2200 h, and a second more sustained surge between 2400 and 0800 h on the morning of estrus. Phen completely depressed the proestrous surge of both gonadotropins but only partially inhibited the second FSH elevation on the morning of estrus. In ovulatory animals, P alone or combined with 1 or 10 mug E2 restored peak LH levels at 1600 h. FSH levels on proestrus in hamsters treated with Phen plus P peaked at 1800 h, while the addition of 1 mug E2 resulted in increased FSH levels at 1600 h; peak levels in both groups were about half of control values. No proestrous increase was detected in ovulatory animals treated with P and 10 mug E2. FSH levels on estrus in hamsters injected with P alone or in combination with E2 were intermediate between those of controls and animals given Phen only. Levels of LH and FSH in animals treated with a single or double dose of Phen or Phen plus E2 or T were not different during the periovulatory period.

Hypothalamic nuclear estrogen receptors and lordosis behavior in hamsters.

These experiments examined the effects of a high and a low dose of estradiol benzoate (EB) in enhancing lordosis behavior and correlated these effects with the retention of hypothalamic nuclear estrogen receptors (NER) in female hamsters. Ten micrograms EB was significantly more effective in facilitating sexual receptivity in hamsters when it was followed 36 or 48 hr later by 0.5 mg progesterone (P), but not when P was given 24 hr after EB. Low levels of behavioral responses were observed in animals that received P at 24, 36 or 48 hr after 2 micrograms EB. Correspondingly, although the hypothalamic NER levels were equally elevated 24 hr after either a low or a high dose of EB, these receptor concentrations remained high at 36 and 48 hr post EB, only in those animals that received the high estrogen dose. The results of these experiments suggest that the long-term retention of NERs (which is maintained by a single high EB dose) may play an important role in the enhancement of sexual receptivity in hamsters.

The effect of hysterectomy on hormone-induced lordosis behavior in hamsters.

Ovariectomized-hysterectomized (OH) and ovariectomized-sham hysterectomized (OSH) hamsters were tested for lordosis behavior following treatments including either 1, 5, or 10 micrograms estradiol benzoate (EB) in combination with 0.1, 0.25, and 0.5 mg progesterone. Few animals responded at the 1 microgram dose of EB and there were no differences in latency to the first display of lordosis or in the total lordosis duration among responding animals in the 5 and 10 micrograms EB groups. However, there was significantly more positive tests in the OSH group injected with 5 micrograms EB than in the OH group and this difference approached statistical significance in the 10 micrograms EB groups. The results are compared to similar studies in rats and possible mechanisms for the effects of hysterectomy are discussed.

Effects of mother-litter separation and reunion on maternal aggression and pup mortality in lactating hamsters.

This study examined the effects of a 24 hr mother-litter separation on maternal aggression and pup mortality in hamsters. There were four lactating groups tested for aggression in their home cages on days 5 and 15 postpartum: a group that was separated from their litters for 24 hr, a group that was not separated from their litters and two 24 hr separation groups in which the litters were returned 30 and 120 min prior to the aggression test. Nonreceptive, estrous cycling animals were used as controls (tested twice, 10 days apart) and as intruders. Measures of aggression recorded during the 10 min tests included the number of attacks, fights, chases and intruder retreats. Pup mortality was examined in the 4 lactating groups and in two additional non-tested groups, one of which was separated from their litters for 24 hr. Lactating hamsters initiated significantly higher levels of aggression than control animals. Mother-litter separation (24 hr) significantly decreased levels of aggression and these levels were restored when litters were replaced 30 and 120 min prior to aggression tests. There were few differences in levels of aggression between days 5 and 15 of lactation. Pup mortality was significantly greater between days 5-6 and 15-16 of lactation among those groups that were separated from their litters compared to those groups that were not separated. Significantly higher mortality levels were found between days 7 and 15 of lactation among the 2 groups in which pups were returned prior to the aggression test compared to all other groups.

Nuclear estrogen receptor binding in microdissected brain regions of female rats during pregnancy: implications for maternal and sexual behavior.

Previously, we showed that changes in nuclear estrogen receptor (NER) concentrations within large dissections of the preoptic area and hypothalamus of pregnant rats might underlie changes in both maternal and sexual behaviors. To more precisely localize these biochemical changes, NER concentrations were measured in microdissected nuclei within the preoptic area and hypothalamus of pregnant rats on days 8, 16 and 22. Results indicated that NER levels changed significantly throughout pregnancy and that the magnitude and direction of change was site specific. Although a different pattern of change was found in each nucleus, NER levels in most preoptic area nuclei were significantly higher by the 16th day of pregnancy compared to those on day 8, while receptor levels in most hypothalamic nuclei did not increase until day 22 of pregnancy. The higher NER levels found in preoptic area nuclei of female rats as pregnancy advances can be correlated with growing maternal responsiveness during pregnancy, while elevated concentrations of NER in hypothalamic nuclei at the end of pregnancy may indicate preparation for postpartum estrus.

Evidence for the involvement of prolactin in the maternal behavior of the hamster.

The hormonal basis of maternal behavior in the hamster has not been clearly established. Treatment of parturient females on the day of delivery with the prolactin release inhibitor, bromocriptine, resulted in a significant disruption of maternal responsiveness at doses as low as 0.5 mg When pregnant females were implanted with ectopic pituitary grafts under the kidney capsule on day 8 or 9 of gestation to elevate circulating prolactin levels, there was no disruption of maternal behavior after bromocriptine injection on the day of delivery. Taken together, these data indicate that prolactin may be an important modulator of the natural onset of maternal behavior at parturition in the hamster.

Hysterectomy-induced maternal behavior during pregnancy in the rat.

Hysterectomies were performed between the 10th and 19th day of pregnancy, and females were tested with pups for the onset of maternal behavior starting 0,24, 48, or 72 hr after surgery. Pups remained with the females overnight, and testing was repeated daily with fresh pups until females exhibited maternal behavior. Latencies for the onset of maternal behavior were shorter after hysterectomy on the 10th and 16th days of pregnancy than in intact pregnant females at the same stages of pregnancy; latencies became shorter, the later the termination of pregnancy. When the ovaries were removed along with hysterectomy during pregnancy, short-latency maternal behavior no longer was exhibited. Pregnant females were tested during the last 40 hr of pregnancy: nest building began at 34 hr prepartum and retrieving at 28 hr prepartum. The effect of hysterectomy during pregnancy on ovarian secretion of estrogen and progesterone is reviewed, and it is concluded that the rise in estrogen secretion, which follows hysterectomy during pregnancy, is most likely the cause of the rapid onset of maternal behavior after hysterectomy. A similar proposal is made for the prepartum onset of maternal behavior in intact pregnant females.

Nuclear estrogen receptor binding in the preoptic area and hypothalamus of pregnancy-terminated rats: correlation with the onset of maternal behavior.

Terminating the pregnancies of female rats on day 16 (D 16) by hysterectomy and ovariectomy (HO) and administering estradiol benzoate (EB) systemically or centrally into the medial preoptic area (MPOA) stimulates the onset of maternal behavior 48 h later. Since estrogen's effects are mediated through its intracellular receptors, the present studies measured nuclear and cytosol estrogen receptor concentrations in the POA and hypothalamus (HYP) of female rats during the 48 h when estrogen is active in stimulating maternal behavior. A low dose of EB (5 micrograms/kg) was used which was effective in stimulating maternal behavior in D16HO females but not in nonpregnant HO females of two types. In D16 animals there was a significantly higher concentration of nuclear receptors in the POA than in the HYP at time 0 (before HO and EB) but thereafter levels were similar in the two areas: nuclear receptor levels rose between 6 and 24 h after which they declined. In nonpregnant females, nuclear receptor levels at time 0 were low in both brain regions, rose significantly between 0 and 24 h, and significantly declined between 24 and 48 h similar to the D16 females. There were minimal differences in cytosol receptor levels among all groups at any time. Results from additional groups, nonpregnant HO females given 100 micrograms/kg EB and D16H animals (females whose pregnancies were terminated by hysterectomy only and their ovaries left intact), both of which exhibit maternal behavior at 48 h, support the idea that a high level of nuclear estrogen receptors in the POA followed by a sustained high level is necessary for estrogen stimulation of maternal behavior.

The role of the uterus in regulation of heat duration in cycling rats.

These experiments examined the effects of hysterectomy on heat duration and on the reinduction of estrous behavior by progesterone (P) following the termination of spontaneous heat in 4-day cycling rats. Hysterectomy did not affect the onset of estrus but prolonged heat duration. The average duration of sexual receptivity for hysterectomized (H) and sham-hysterectomized (SH) rats was 18.2 and 13.0 hr, respectively. Furthermore, H animals injected with either 0.5 mg P within 2 hr, or 4.0 mg P 24 hr following the termination of natural estrus showed significantly higher lordosis and solicitation responses than SH rats similarly treated. These behavioral findings were correlated with the level of hypothalamic progestin receptors. That is, H animals had a significantly higher concentration of progestin receptors than SH rats immediately following the termination of spontaneous heat and also 24 hr later. Both in estrous-cycling rats and in gonadectomized animals treated with estradiol benzoate (EB), hysterectomy resulted in higher serum estradiol (E2) levels. The results of these experiments suggest that prolongation of the period of sexual receptivity and the facilitated behavioral responses to P following the cessation of estrus in hysterectomized animals may be due to a lowered clearance rate of circulating estradiol which presumably enhances the estrogen conditioning of the neural substrates.

Effects of pregnancy hormones on maternal responsiveness, responsiveness to estrogen stimulation of maternal behavior, and the lordosis response to estrogen stimulation.

The aim of the study was to determine whether there is an increase in responsiveness to estrogen stimulation of maternal behavior and lordosis responsiveness during pregnancy. Using separate groups of pregnancy-terminated females, we measured the initial maternal responsiveness of hysterectomized-ovariectomized (HO) females and their responsiveness to estrogen stimulation. Maternal behavior latencies were studied in females HO on the 8th, 10th, 13th, 16th, or 19th day of pregnancy (8HO-19HO) and in nonpregnant HO (NPHO) females. Groups were injected sc with estradiol benzoate (EB) in doses ranging from 0 to 200 microgram(s)/kg and tested for maternal behavior (retrieving, crouching, and licking pups). In addition, we investigated whether there is an increase during pregnancy (following HO) in lordosis responsiveness to estrogen stimulation. Lordosis behavior was studied in pregnant HO females (days 8, 16, and 22) and NPHO females given 0 to 200 microgram(s)/kg EB. There was an increase in maternal responsiveness in oil-treated HO females starting around midpregnancy. From early pregnancy on there was also an increase in maternal responsiveness to 20 microgram(s)/kg EB. In late pregnant females (16HO) there was a further increase with 50 microgram(s)/kg EB. There was no increase in lordosis responsiveness to EB stimulation during pregnancy; pregnant and nonpregnant HO females had the same EB threshold for stimulating lordosis behavior. The results of both studies were related to increases during the latter half of pregnancy in nuclear estrogen receptor concentrations in the MPOA, an area that mediates estrogen stimulation of maternal behavior, and the absence of such increases during pregnancy in the VMH, an area that mediates estrogen stimulation of lordosis behavior.