Pre- Pubertal Adult Peri- Post-

pubertal menopause/ menopause/

estropause estropause

Figure 43.3 A summary of estrogen release across the life cycle in humans, nonhuman primates, rats, and mice. Please note that avians are excluded due to the variability within their group. In these species, estrogen concentrations increase during the pubertal period and are at high levels in adulthood. Declines in estrogen are precipitous in humans, monkeys, and mice, although they occur at different relative times in the life cycle. In rats, the estropause is characterized by continued high estrogen levels and a persistent estrus vaginal cytology until much later in life.

Estrogen preovulatory surge, and decreases in LH^ subunit mRNA expression during the GnRH/LH surge and following OVX (Rubin, 2000; Wise et al., 2002). However, evidence for hypothalamic involvement in rodents is by far the most compelling reason for using this model of reproductive aging. Transplantation of ovarian tissue from acyclic, aged rats into young females showed that these ovaries can support regular estrous cycling, whereas transference of young ovarian tissue into aged animals showed no resumption of cyclicity. A similar experiment confirmed this for mice as well (Rubin, 2000). Taken together, these studies provide evidence for an age-dependent change in the hypothalamic-pituitary axis that causes a disruption in the normal estrous cyclicity, and suggests that this mechanism may supersede the observed changes in ovarian morphology. Additionally, electrophysiological stimulation of the acyclic, female rat hypothalamus is able to restore function to the reproductive axis (Rubin, 2000), providing strong evidence that a neural aspect contributes to the onset of estropause. Thus, the rodent model has become an important contributor to studies of neuroendocrine influences on reproductive function.

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