Estrogen dynamics in the female rhesus monkey

The metabolic clearance rates (MCR) and interconversions [( rho]BB) values for estrone (E1) and estradiol (E2) in female rhesus (Macaca mulatta) monkeys on Days 9, 14, and 23 of the menstrual cycle were measured using constant infusions of [3H] estradiol and [14C] estrone. The menstrual cycles in these monkeys were reproduced by using Silastic capsules of E2 and progesterone after bilateral ovariectomy. The serum levels of E2 and progesterone were measured by radioimmunoassay and were similar to those for the intact menstrual cycle. The MCR of E2 on Day 14 (52.8 +/- 6.8 l/day/kg) was significantly greater (p less than 0.05) than that measured on Day 9 (31.1 +/- 3.6 l/day/kg) or Day 23 (35.4 +/- 2.1 l/day/kg). The MCR of E1 was also different (p less than 0.05) on Day 14 (77.6 +/- 14.9 l/day/kg) compared to the values on Days 9 and 23 (50.2 +/- 4.9 and 48.2 +/- 3.9 l/day/kg, respectively. There was no change in percentage of free E2, percentage of albumin-bound E2, or sex hormone-binding globulin levels on those 3 days of the cycle. The interconversions between E2 and E1 were not influenced by the day of the cycle. We conclude that the high levels of E2 occurring at the time of the E2 peak result in increases in the MCRs of both E2 and E1 that are not associated with changes in the pattern of protein-binding or in the activity of the 17 beta-hydroxy steroid dehydrogenase.     

Menopause in female rhesus monkeys

Fifteen female rhesus monkeys (Macaca mulatto), ranging in age from 8 to 34 years, were studied for one year to characterize the endocrine and menstrual changes associated with menopause in this species. Five monkeys were premenopausal; these younger monkeys, ages 8–11 years, menstruated and showed cyclic ovarian activity during the 12–month study period, as evidenced by menses and periodic elevations of serum estradiol (E₂) and luteinizing hormone (LH) concentrations. Four females, ages 24–26 years, were in transition to menopause. Two of these perimenopausal females menstruated and secreted E₂ and LH in a periodic fashion; the other two females showed elevated LH concentrations, consistently low E₂ levels, and no evidence of menstruation. Six females, ages 27–34 years, were clearly postmenopausal; LH concentrations were high, whereas E₂ concentrations were uniformly low. There was a significant inverse correlation between basal E₂ concentrations and age, and a significant positive correlation between age and LH concentrations across all 15 animals. Hormonal changes indicative of ovulation, when they occurred, were generally restricted to the winter and early spring months. Histological analysis of ovaries from four postmenopausal females revealed little or no evidence of active folliculogenesis. These data indicate that menopause in female rhesus monkeys does not occur until the second half of thethird decade of life. © 1995 Wiley-Liss, Inc.     

Estimation of body fat in female rhesus monkeys

Measurement of height (crown–rump length), body weight, and abdominal subcutaneous fat depth, based on skinfold thickness taken from 13 female rhesus monkeys comprising two age groups were correlated with body fat values derived from tritiated water determinations of total body water. The manner with which each measure was related to percent body fat differed as a function of age of the animal. In the young, nulliparous females, crown–rump length was the single best predictor of body fat, whereas in the older, multiparous females, skinfold thickness correlated most highly with body fat. When all measurements, including the Quetelet index [(wt/ht)² × 1,000], were combined statistically and regressed against percent body fat, a significant increase in predictive ability was obtained. When each age group was considered separately, the resulting equations again reflected the agegroup biases. In addition, as an internal check on the validity of the regression equations, an additional regression analysis was performed using morphometric data from selected animals in each age group. These equations yielded accurate estimates of body fat when compared to determinations made from total body water. These analyses indicate that the predictive accuracy of morphometric data is greatly enhanced by using these measurements in concert. Furthermore, the utility of such predictions is influenced by the specific physical characteristics of the subject population.     

Menstrual cycle characteristics of seasonally breeding rhesus monkeys

Rhesus monkeys in seminatural environments exhibit a distinct seasonal mating cycle with conceptions restricted to the fall and winter months. In the present study, the characteristics of menstrual cycles were examined during a 1-year period in twelve rhesus monkeys in whom pregnancy was prevented. Menses occurred throughout the year, but ovulations were observed only in the fall and winter months. Menses in the spring and summer months occurred irregularly and were associated exclusively with anovulatory cycles. The total number of ovulations exhibited by these females during the breeding season ranged from two to six and was positively related to body weight, mean luteal phase progesterone (P) levels of normal cycles and social dominance rank. Ovulations with a short luteal phase were exhibited by four females (seven cycles), with the likelihood of occurrence increasing as the breeding season progressed. The incidence of abnormal cycles was predicted from the linear combination of parity, body weight and luteal phase P of normal ovulatory cycles. These results suggest that during the seasonally delimited period of ovulation, females exhibit a range in the quality and quantity of ovulations which may be predicted by certain idiosyncratic physical and behavioral traits.     

Comparative pharmacokinetics of frusemide in female rhesus monkeys, cynomolgus monkeys and baboons

1. The pharmacokinetics of frusemide have been compared in 3 non-human primate species after single intravenous dose of 3 mg/kg of the drug. 2. Peak mean plasma concentrations of frusemide were 31.6, 33.6, 43.6 micrograms/ml in the rhesus monkey, cynomolgus monkey and baboon respectively, and concentrations declined with a half-life of about 20 min. 3. There were no notable differences in the pharmacokinetic parameters estimated from either a one-compartment or two-compartment open model. 4. There were statistically significant species-related differences in clearance, half-lives and volumes of distribution adjusted for bodyweight. 5. The pharmacokinetics of frusemide in the cynomolgus monkey are closer to those in man than are those in the rhesus monkey, the baboon or other commonly used laboratory animal species.     

Ultrasonographic assessment of the endometrium in rhesus monkeys during the normal menstrual cycle

This study was undertaken to determine whether cyclical changes in the endometrium of the rhesus monkey could be observed by using ultrasound. Three indices of endometrial size were examined: the antero-posterior (or ventro-dorsal), longitudinal, and transverse diameters. Changes in the ultrasonic reflectivity of the endometrium were also assessed. We have attempted to correlate these endometrial parameters with the hormonal status of the animal. Ultrasonography was performed for an average of 12 consecutive days during 19 menstrual cycles. All ultrasonic recordings were normalized to the day of the estradiol (E2) peak (Day 0). We found that the reflectivity of the endometrium was dependent on the stage of the cycle: during the follicular phase, the endometrium appeared less echogenic (darker) compared to the myometrium; in the luteal phase, the endometrium was more echogenic (lighter). During the follicular phase (Days -9 to 0), there was a linear increase in the antero-posterior (p less than 0.001), longitudinal (p less than 0.05), and transverse (p less than 0.001) diameters. In the luteal phase (Days 1-15), no significant changes were observed in these diameters. An estimated endometrial volume (EEV) was obtained by the product of the antero-posterior, longitudinal, and transverse diameters. Each animal observed during the follicular phase (n = 14) exhibited a peak in the EEV, which correlated with the day of the E2 peak (p less than 0.01). From this study, we conclude that the sonographic appearance of the endometrium of the rhesus monkey reflects the cyclical changes that occur during the menstrual cycle.(ABSTRACT TRUNCATED AT 250 WORDS)     

The relationship between aggressive behavior and menstrual cycle stage in female rhesus monkeys (Macaca mulatta)

The aggressive behavior of eight adult female rhesus monkeys, living in a captive social group, was studied prior to and during a breeding season extended by vasectomizing all the adult males in the group. Female reproductive status was ascertained by: recording all adult female-adult male copulations, detecting menstruation by vaginal swabbing, and analyzing serum progesterone levels by radioimmunoassay. Females were more aggressive during the follicular stage of their menstrual cycle than the luteal stage or during the period prior to the onset of seasonal ovarian activity. Increases in aggression were limited to increases in the milder forms of agonistic behavior, primarily threatening gestures. Although the females showed their highest rates of noncontact aggressive response categories during the follicular stage, several showed highest rates of contact aggressive response categories in the precycling period.     

The similarity principle underlying social bonding among female rhesus monkeys

Twenty adult female rhesus monkeys (Macaca mulatta) were observed over a three-year period. They lived in a mixed captive group with kinship relations known for three generations. The study's aim was to test Seyfarth's [J. theor. Biol. 65: 671-698, 1977] model of rank-related grooming and to investigate two other possible determinants of social bonding, i.e. relative age and the group's stratification into two social classes. Data on affiliation, coalitions, and social competition were collected by means of both focal observation and instantaneous time sampling. Whereas certain elements of the existing model were confirmed, its explanatory principles were not. Social competition did not result in more contact among close-ranking females (the opposite effect was found), and the relation between affiliative behavior and coalitions was more complex than predicted. Based on multivariate analyses and a comparison of theoretical models, we propose a simpler, more encompassing principle underlying interfemale attraction. According to this 'similarity principle', rhesus females establish bonds with females whom they most resemble. The similarity may concern genetical and social background, age, hierarchical position and social class. Effects of these four factors were independently demonstrated. The most successful model assumed that similarity factors influence female bonding in a cumulative fashion.     

Estrogen plus androgen induced mounting in adult female hamsters

This study demonstrated that the combined administration of estrogens and androgens activates the display of mounting by female hamsters. Forty-nine ovariectomized hamsters were injected daily with either estradiol benzoate (EB, N = 8); dihydrotestosterone propionate (DHTP, N = 7); testosterone propionate (TP, N = 6); androstenedione (AD, N = 9); EB plus DHTP (N = 10); or estrone plus DHTP (E₁ + DHTP, N = 9). All androgens were administered at a dose of 1 mg per day for the first 24 days and at a dose of 2 mg per day for the last 14 days. The EB dose was 6 μg per day and the E₁ dose was 100 μg per day. Females were tested for male behavior once a week starting on Day 10 of injections and for female behavior on Day 39.One hundred percent of EB + DHTP treated females; 67% of the E₁ + DHTP treated females; 55% of the AD treated females; 33% of the TP treated females; 29% of the DHTP treated females; and none of the EB treated females mounted during at least one test. Only one of the E₁ + DHTP treated females showed the intromission pattern; otherwise most females which mounted displayed the intromission pattern. The median number of days preceding the onset of mounting ranged from 21 to 31 days and did not differ among treatment groups.     

Age- and dominance-related variation in feeding time among free-ranging female rhesus monkeys

Observations were made on the feeding behavior of 34 lactating rhesus females (Macaca mulatta) at Tughlaqabad, India. Consistent interindividual differences in feeding times were found and two sources of this variation were identified. Time spent feeding was found to decline with female age; rhesus mothers 4–6 years old spent over 40% more time feeding than did females 11–15 years of age. When the animals were divided into high- and low-status groups, dominance was also found to relate to individual feeding times; high-status females spent more time feeding that did low-status females, but this difference was evident only when the effect of female age was held constant. The age effect is probably an expression of age-related variation in nutritional requirements due to growth in the youngest subject and, perhaps, a declining basal metabolic rate in the oldest. We speculate that the comparatively weak dominance effect is due less to the aggressive interruption of feeding bouts than it is to a presumed greater vigilance on the part of subordinant mothers in monitoring their infants' whereabouts.     

Ovarian hormones and food intake in female guinea pigs and rhesus monkeys

Food intake was measured during ovarian cycles of female guinea pigs and rhesus monkeys. In both species, the period of lowest food intake occurred around the expected time of ovulation. Feeding levels were lowest in the guinea pig during the time of estrus, estrus being estimated on the basis of vaginal membrane changes. Minimum food intake in the rhesus occurred prior to the midpoint of the menstrual cycle, on Day 13, approximately 15–16 days before the next menstruation. In ovariectomized females of both species, either multiple or single estradiol injections significantly lowered food intake. Single progesterone injections to such females were found to have no significant effect on levels of feeding.     

Persistent adrenocortical activation in female rhesus monkeys after new breeding groups formation

Persistent elevated adrenocortical responsiveness to ACTH has been demonstrated in female rhesus monkeys as long as 13 weeks after relocation into new single male breeding groups. Measures of immediate responses to psychosocial stress of grouping such as aggressive interaction and circulating plasma cortisol levels were highest immediately after grouping, but tended to decline to lower levels after the first month. In a retrospective comparison of such 'new' breeding groups (less than one year) versus established breeding groups (more than two years), stress-related morbidities such as trauma (wounding) and loose stools were higher for as long as six months after new group formation. The actual and potential adverse effects of regrouping stress on colony health and reproduction are relevant to cost-benefit assessment of such colony management procedures.     

Proceptive behavior of female rhesus monkeys during tests with tethered males

Proceptive behavior of female rhesus monkeys during follicular and luteal phases of the ovarian cycle was examined in laboratory tests with a tethered male partner. Cyclical changes in proceptive behavior were observed. In tests during the follicular phase of their cycles, females on the average approached and solicited the male at a higher rate, spent more time sitting within proximity of him, and less time at a maximum distance away from him than during tests in the luteal phase of their cycles. Additionally, in the follicular phase of their cycles, females exhibited an increase in proceptivity following the male's ejaculation. This latter finding was discussed in light of other observations demonstrating that male rhesus monkeys are capable of multiple ejaculations. When females were paired with a tethered, ovariectomized female as a partner, rather than an adult male, none of the cyclical changes in proceptive and sexual behavior were observed.     

Dose-response data for X-ray induced translocations in spermatogonia of rhesus monkeys

The yields of translocations in spermatocytes after irradiation of spermatogonia of Rhesus monkeys with doses of 100, 200 or 300 rad X-rays were low, and consistent with a humped dose-response curve with a peak at about 200 rad. Such a curve would agree well with earlier results on the marmoset and man, but the yields at any dose in the Rhesus monkey were lower.     

Self-agency in rhesus monkeys

Rhesus monkeys (Macaca mulatta) have shown the ability to monitor their own mental states, but fail the mirror self-recognition test. In humans, the sense of self-agency is closely related to self-awareness, and results from monitoring the relationship between intentional, sensorimotor and perceptual information. Humans and rhesus monkeys were trained to move a computer icon with a joystick while a distractor icon partially matched their movements. Both humans and monkeys were able to monitor and identify the icon they were controlling, suggesting they have some understanding of self-agency.     

Effects of estradiol and aging on fine manual performance in female rhesus monkeys

Aging is characterized by a progressive deterioration of motor function related to dysfunctions of the nigrostriatal system. Because estrogen has been reported to protect dopaminergic neurons and to improve the motor deficits associated with Parkinson's disease, we hypothesized that it would partially reverse the age-related decline of motor function in normal aging. We tested the effects of estrogen treatment and withdrawal on fine motor performance in five aged (21-24 years old) and five young (6-9 years old) ovariectomized female rhesus monkeys. The tests required the monkeys to use each hand to retrieve a Life Saver candy from metal rods bent in shapes of different complexity. Monkeys were tested twice a week for 8 consecutive weeks, during treatment with placebo or ethinyl estradiol (EE(2)) in alternating 14-day blocks. Each behavioral test was videotaped and subsequently scored for the duration and the success of the first trial on each shape. Both groups of monkeys improved rapidly with practice in speed and success of retrieval. The older monkeys were slower but as successful as the young monkeys in retrieving the candy. The left hand was faster than the right hand for both the aged and young females. We failed to detect any effect of EE(2) treatment on speed or success of retrieval in either group. These results confirm the slowing of fine motor performance with aging in female rhesus monkeys. They also indicate that estradiol, at least as administered in this study, does not benefit fine manual performance.