Reproductive endocrinology of wild female chimpanzees (Pan troglodytes schweinfurthii): methodological considerations and the role of hormones in sex and conception.

Fecal and urine samples were collected from 81 female East African chimpanzees (Pan troglodytes schweinfurthii) in three major study populations in Gombe National Park, Tanzania, and Budongo Forest Reserve and Kibale National Park, Uganda. In this study I evaluated issues related to sample storage and assay reliability, and used these methods to investigate the significance of ovarian hormone levels in terms of conception success and sexual behavior. Drying of feces proved to be an effective technique and resulted in hormonal concentrations that were significantly correlated with concentrations in frozen feces. Estimates of ovarian steroid production based on urine and fecal sampling were significantly correlated with each other. The ovarian cycle profiles obtained, which were aligned relative to sexual swelling detumescence, corroborate previous findings in wild west African chimpanzees [Deschner et al., Animal Behaviour 66:551-560, 2003] in suggesting that the fertile period is limited to the last week of tumescence, but that ovulatory timing is not as precise as previously thought. A comparison across cycles confirmed the hypothesis that higher ovarian steroid levels are associated with an increased probability of conception. Females that did conceive with relatively low hormone levels had poor reproductive outcomes. Sexual behavior was tied to the probability of conception both within and across cycles. Copulatory activity within cycles closely followed the estrogen profile and was timed to coincide, on average, with the peak fertile period of females. Further, rates of copulation were significantly higher during the fertile periods of cycles that led to conception than those that did not.

Peripartum sex steroid changes and maternal style in rhesus and Japanese macaques.

The subtle and complex relationships between the sequential maturation of the endocrine systems during pregnancy and parturition, and the hormonal role in activating the central nervous system to express maternal behavior in primates, are far from being completely understood. Recent studies on the association between sex steroids and maternal behavior have yielded conflicting results in this group. Here we use a comparative approach to assess the correlation between changes in the peripartum endocrine profiles and maternal styles in two closely related macaque species, housed in analogous environments. We included in this study the first seven Japanese macaque and seven rhesus macaque mother-infant pairs born during the birth season of 2001 at the Primate Research Institute, Kyoto University, Japan. We observed each pair 3h/week (six weekly 30-min observation sessions) during the first 12 weeks of lactation. We collected fecal samples twice a week from each mother, starting 4 weeks before parturition and ending 4 weeks after parturition. We tested the hypothesis that neuroendocrine changes during pregnancy and lactation might specifically contribute to the regulation and timing of infant rejection. Despite their biological similarities, we observed a clear difference in maternal style between the two groups concerning rejection rates: rhesus macaque mothers rejected their infants earlier and more frequently throughout the whole 12 weeks of study. On the other hand, protectiveness showed similar patterns and values in the two groups, and maternal warmth was significantly higher in the rhesus group, but it followed a similar pattern over time. We also confirmed an association between maternal rejection and excreted estrogen, but not excreted progesterone, for Japanese macaques. This association was not apparent for the rhesus macaques. This result, coupled with the observation that rhesus mothers are more rejecting than Japanese macaque mothers, tends to support our hypothesis. As a group, rhesus macaques are less inhibited in the rejection of their infants, and this is paralleled by a less marked change in the primacy of estrogen in the last phase of pregnancy. On the contrary, the Japanese group is characterized by higher levels of E(1)C and the E(1)C/PdG ratio. Therefore, according to our hypothesis, their tendency to increase the rejection rate may be suppressed through a feedback loop that enhances maternal motivation and results in a more tolerant outcome toward the infant.

Urinary steroids, FSH and CG measurements for monitoring the ovarian cycle and pregnancy in the chimpanzee.

Non-invasive methods for monitoring reproductive status of chimpanzee based on the measurement of urinary steroids and gonadotropins were examined. A typical pre-ovulatory urinary estrone conjugate (E1C) surge and post-ovulatory increase in pregnandiol glucuronide (PdG) were seen during the menstrual cycle. Urinary follicle stimulating hormone (FSH) showed two peaks over the infertile menstrual cycle. The earliest changes indicating pregnancy were a coincident rise in E1C and chorionic gonadotropin (CG) levels and a concomitant fall in FSH levels. Urinary PdG levels showed a prolonged rise. Urinary E1C in the pregnant chimpanzee was higher than during the menstrual cycle and increased with advancing gestation, with maximum levels occurring near term. In the case of stillbirth, E1C and CG levels from mid- through late-pregnancy were low and the prepartum progressive increase in E1C was not shown. The data presented here are of great practical value in captive breeding management of chimpanzees.

Studies of molecular structure parameters of 20-piperidin-2-yl-5alpha-pregnan-3beta,20-diol and its N-methyl derivative: two inhibitors of Delta24(25) sterol methyl transferase and Delta24(24') sterol methyl reductase of Trypanosoma cruzi.

Molecular structural parameters of two potential drugs against Trypanosoma cruzi epimastigotes, 20-piperidin-2-yl-5alpha-pregnan-3beta,20-diol (1) and 20-N-methylpiperidin-2-yl-5alpha-pregnan-3beta, 20-diol (2) were studied using a combination of a stereoselective synthetic route, spectroscopic characterization and single-crystal X-ray analysis. Both compounds were synthesized with an R configuration at C20. This chirality is a consequence of the stereoselectivity observed during the formation of the intermediate 20-pyridin-2-yl-5alpha-pregnan-3beta,20R-diol (4). NMR data indicated that the six-membered aza ring of (2) is conformationally more restrained, in CDCl3 solution, than (1). X-ray studies showed that maximum deviations among structural molecular parameters of (1) and (2) correspond to torsion angles along the C20-C22 bonds, leading to a different relative orientation of the N atom; a critical structural parameter for the binding properties of aza-sterols to Delta(24(25)) sterol methyl transferase. Cremer-Pople parameters of the five-membered rings of (1) and (2) lie in the observed range for a family of tetracyclic fused ring systems retrieved from the CSD. The phi2 parameter of (1) lies just on the mean of the family, while phi2 of (2) deviates significantly towards the lower limit.

Relationship of pregnanediol level to cognitive behavior and mood.

This work examines data secured from a larger study relating cognitive behavior and mood in women to variation in estrogen level. The larger study noted that performance tended to be better during the luteal phase. The present analysis looks at the relationship of urinary pregnanediol levels with mood and cognitive behaviors. Thirty women with non-oral contraceptive-controlled menstrual cycles were tested during the luteal phase on a battery of cognitive tests and a variation of the Clyde Mood Scale. The cognitive tests were selected based upon the automatization versus perceptual restructuring dimensions described by Broverman and colleagues. Pregnanediol levels were measured in 24-hour urine specimens collected on the same day. Results show a significant relationship of pregnanediol level with mental subtraction and with time estimation. Perceptual restructuring tasks in general (perceptual restructuring index) showed a significant positive relationship with pregnanediol levels. Mood, however, was not found to be related to pregnanediol levels.

Hormones and human milk.

The presence of several hormones in milk occurring either by passive diffusion or by active concentrating mechanism from blood can be of great concern to the neonate. According to Fulkerson [1979] when the clearance rates of the hormones out of blood is considered, this worry is unwarranted. Concerning the steroids, when their levels have been monitored in milk after lactogenesis, the worry for the baby seems to be unfounded. But with the new finding of high level of LH-RH in milk whose concentration far exceeds that of blood, care should be taken to examine in the neonates whether the levels of LH and FSH become disproportionately high and induce the secretion of gonadal steroids at a higher level.

PIP: The presence of several hormones in milk occurring either by passive diffusion or by active concentrating mechanism from blood can be of great concern to the neonate. According to Fulkerson, when the clearance rates of the hormone out of blood is considered, this worry is unwarranted. Concerning the steroids, when their levels have been monitored in milk after lactogenesis, the worry for the baby seems to be unfounded. However, with the new finding of new levels of luteinizing hormone-releasing hormone in milk whose concentrations far outweigh that of blood, care should be taken to examine whether the levels of luteinizing hormone and follicle stimulating hormone become disproportionately high in the neonate and induce the secretion of gonadal steroids at higher levels.