Patricia L. Whitten

Response of fecal cortisol to stress in captive chimpanzees (Pan troglodytes)

This study examined whether fecal cortisol could be used as an index of stress responses. The stress responsiveness of fecal cortisol was tested with a stressor known to stimulate adrenal activity, the stress of anesthesia. Daily fecal and urine samples were collected from four captive chimpanzees (Pan troglodytes) before and after anesthetizations with Telazol®/Ketasat®. Tests of assay validity indicated that cortisol was measurable in chimpanzee fecal extracts. Fecal cortisol concentrations were significantly elevated 2 days after anesthetization, with elevations in seven of the eight treatments. The posttreatment peak was significantly greater than baseline values in three of the four subjects. Both fecal concentrations and proportionate increases in response to stress were significantly correlated with the corresponding values in urinary cortisol, confirming the stressfulness of these procedures and the stress responsiveness of fecal cortisol. These findings provide evidence for the application of fecal cortisol as a noninvasive index of physiologic stress in nonhuman primates. Am. J. Primatol. 44:57–69, 1998.

Effects of a phytoestrogen diet on estrogen-dependent reproductive processes in immature female rats

The study reported here examined the effects of a phytoestrogen diet on progestin receptor induction, vaginal opening, and the onset and maintenance of vaginal cycles in developing female rats. A natural dietary concentration (0.01%) of the isoflavonoid coumestrol was incorporated into the AIN semipurified diet and fed from 21 to 24 days (acute treatment) or from 22 to 60 days (chronic treatment). Progestin receptor induction was observed in the uterus, pituitary, and hypothalamus-preoptic area following acute treatment. Responses were more marked in the uterus and pituitary than in the hypothalamus-preoptic area. Vaginal opening was accelerated by 4 days during chronic coumestrol treatment and occurred at a lighter body weight. Vaginal cycles began on vaginal opening and did not differ in regularity from those of control animals. However, irregular cycles were observed in coumestrol-treated animals at 116 to 131 days, suggesting that chronic coumestrol treatment may have induced some permanent changes in reproductive function. These findings demonstrate that plant estrogens, at natural dietary levels, produce significant, agonistic actions in several estrogen-dependent tissues and processes.

Effects of a normal, human-concentration, phytoestrogen diet on rat uterine growth

The estrogenic action of the prototype natural phytoestrogen coumestrol was examined in rats in in vitro and in vivo tests. To establish the binding specificity of coumestrol and its relation to biological activities, saturation analyses and uterine weight assays were performed. These assays indicated that coumestrol competitively inhibited binding to the estrogen receptor and induced increases in uterine weight in keeping with its estrogen receptor affinity constant. Most importantly, coumestrol was uterotrophic when incorporated in a semipurified diet at natural dietary concentrations. Significant increases occurred in both uterine wet weight and dry weight, indicating that coumestrol produces true uterine growth. Effects appeared to be cumulative, raising questions of time-related interactions with other estrogen-sensitive mechanisms and clearance of isoflavonoids. Coumestrol induced uterine growth over a 90-hour period at dietary concentrations of 0.01 to 0.1%. Lower doses not active over this period were active when provided over a longer period of time: a 0.005% concentration was not active over a 90-hour period, but was active when provided over a 180-hour period. Coumestrol-induced uterine growth was accompanied by the induction of cytosolic progestin receptors and increases in nuclear estrogen binding. Scatchard analyses verified that these changes were due to changes in receptor number. These studies show that the naturally occurring phytoestrogens have dramatic estrogenic effects at natural dietary levels. These actions may be expressed via traditional receptor-mediated actions and therefore may have the same implications for development, health, and disease as do the steroidal estrogens produced by the body. Because rats have no sex hormone-binding globulin, further studies must be conducted in humans. However, these findings suggest that the natural dietary phytoestrogen coumestrol is a potent estrogen that must be considered in calculating the total estrogenic load to which humans are exposed during normal life.

Phytoestrogen Influences on the Development of Behavior and Gonadotropin Function

Abstract The effect of phytoestrogens on the sexual differentiation of gonadotropin function was examined by neonatal exposure of pups through milk of rat dams fed a coumestrol (100 μg/g), control, or chow diet during the “critical period” of the first 10 postnatal days or throughout the 21 days of lactation. In females, exposure to coumestrol throughout the period of lactation produced growth suppression and an acyclic condition in early adulthood resembling the premature anovulatory syndrome. When the period of treatment was restricted to the first 10 postnatal days, however, no effects on vaginal cycliclty were seen. The 10-day exposure period produced more marked effects in males, resulting in transitory reductions in body weight in weanling males and reductions in mount and ejaculation frequency and a prolongation of the latencies to mount and ejaculate. Testicular weights and plasma testosterone levels did not differ among treatment groups, suggesting that the deficits in male sexual behavior were not due to deficits in adult gonadal function. Few effects of chow treatment were observed. However, significant differences from controls were apparent for weight at vaginal opening in females, and mount rate for chow-treated males was intermediate between that of controls and that of the coumestrol-treated group. These data provide evidence that lactational exposure to phytoestrogen diets can alter neuroendocrine development in both female and male rats.

Triadic interactions in Savanna-dwelling baboons

Interactions between adult males and infants may have important consequences not only for males and infants, but also for mothers. Considerable attention has been paid to interactions that involve two males and an infant. Investigators have proposed three different general strategies to account for this behavior: (a) exploitation of the infant for one male’s advantage, (b) protection of the infant from harassment and aggression, and (c) development of relationships with the infant’s mother. We review various accounts of these interactions, detail the hypotheses used to explain the behavior, make predictions derived from the hypotheses, and evaluate available data for testing the predictions. We conclude that multiple factors are probably at work, but the development of social relations between a male and an infant’s mother is a central force.

An Evolutionary Perspective on the Climacteric and Menopause

There appears to be no specific adaptive evolutionary response to estrogen deficiency in postreproductive women. On the contrary, many of the physiological responses to the menopause resemble those seen in the reproductive years, especially during the puerperium. However, responses that are positive adaptations for the puerperium such as calcium and lipid mobilization, increased vigilance and lack of REM sleep, decreased vascular elasticity, and radiation of heat may lead to adverse outcomes during the menopause. We anticipate that improved understanding of the physiological basis of the adverse responses to ovarian failure in the post reproductive woman should furnish more rational educational, preventative, and therapeutic strategies for women during the climacteric/menopause.