Transient Shortening of Estrous Cycles in Aging C57BL/6J Mice: Effects of Spontaneous Pseudopregnancy, Progesterone, L-dihydroxyphenylalanine, and Hydergine1

Abstract

Regular estrous cycles can be reinitiated in old acyclic female rats by pharmacologic, hormonal, and environmental manipulations. The most responsive acyclic states are persistent vaginal cornification (PVC) and spontaneous pseudopregnancy (SP). However, it is not known if the irregular cyclicity that precedes acyclicity during aging can also be alleviated. We found that transient shortening of estrous cycles follows smear sequences indicative of pseudopregnancy in C57BL/6J mice, aged 9-15 mo, suggesting a role for progesterone. This phenomenon was investigated through a limited model of pseudopregnancy in which intact aging mice with lengthened cycles were given progesterone implants (yielding 70 ng progesterone/ml plasma) that suppressed estrous cycles; upon removal of the implants, cycles were transiently shortened in aging mice. Therefore, we hypothesize that withdrawal from the progesterone elevations associated with SP is the mechanism in shortening subsequent estrous cycles. Effects of central-acting drugs, similar to those used to reinitiate cyclicity in acyclic old rats, were also examined. Hydergine, an ergot mixture with partial dopaminergic and serotonergic agonist activities, suppressed SP when fed to 10- to 12-mo-old, middle-aged mice. Hydergine did not otherwise affect estrous cycle length, prevent PVC, or reinitiate cycling in acyclic PVC mice. Feeding L-dihydroxyphenylalanine to middle-aged mice did not suppress SP, affect estrous cycle lengths, or reinitiate cycles from PVC.

Atrazine and reproductive function: mode and mechanism of action studies

“…For example, a loss of the LH surge, which is necessary to maintain cycles, has been attributed to a loss in hypothalamic catecholaminergic (norepinephrine and dopamine) function with age (Wise, 1984; Mohankumar et al, 1995). If the female rodent is treated with catecholaminergic agonists such as l ‐tyrosine (e.g., rat; Watkins et al, 1975; Cooper and Walker, 1979; Forman et al, 1980) or L ‐dopa (e.g., rat; Quadri et al, 1973; or mouse; Cotzias et al, 1977; Flurkey et al, 1987), the ovulatory surge of LH and ovarian cycles are maintained and reproductive senescence is delayed. In these studies, the effects of catecholamine treatment on LH secretion and subsequent ovarian function were the primary focus.…”

Hormonal Influences on the Estradiol-Induced and Age-Related Increases of Pituitary Dopamine in C57BL/6J Mice

“…2). P antagonized the E2-induced increase in pi tuitary DA, but this dose of P (approximately 35 ng/ml plasma, roughly half of the levels seen in mid-pregnancy) [19] did not reduce pituitary DA to levels found in OVX mice: higher doses of P may be required. The age-related increase in pituitary DA in female mice is primarily due to ovarian factors, and eventually returns to young basal values after OVX [41], The attenuation of both the E^-induced and age-related increase of pituitary DA by P is consistent with a primary role of E: in this age change ( fig.…”

“…Unless otherwise stated in the figure legends, plasma E2 from these implants was 15-20 pg E2/ml plasma. The P-containing Silastic implants used in this study yield approximately 35 ng P/ml plasma [19]. When OVX mice were treated with both E2 and P, the E2 and P implants were given si multaneously 3 weeks before sacrifice.…”

Mechanisms and implications of sex differences in cardiac aging

“…While aging female rodents do not undergo true menopause, they do become reproductively incompetent or senescent with advanced age, a state referred to as estropause. Estropause is characterized by persistently lower estrogen, varying length of the estrous cycle, with eventual cessation of cyclicity around 12-14 months of age [ 71 ] . Ovariectomy of aged animals supports the loss of estrogen with aging, as animals do not undergo changes in metabolic function with ovarian estrogen removal, nor do significant changes in cardiac phenotype occur with removal of the ovaries [ 72 ] .…”