To examine the molecular genetic basis for the age-related increase in PRL secretion and decrease in LH production in the rat, we measured steady state levels of PRL and LH/3 mRNA in pituitary homogenates and cell lysates from monolayer adenohypophyseal cultures. These mRNA levels were compared with the corresponding levels of immunoreactive PRL and LH in sera and culture media. Paired groups (n = 4-10/group) of intact and 4-week ovariectomized mature (6-7 months old) and old (23-25 months old) female Wistar rats were studied. Serum PRL levels were 550% higher in intact old us. mature rats (P < 0.001), whereas the corresponding pituitary homogenate levels of PRL mRNA were similar (P > 0.4). Medium PRL concentrations were 230% greater (P < 0.006) whereas cell lysate concentrations of PRL mRNA were unaltered (P > 0.2) in monolayer cultures from intact old vs. mature rats. Serum PRL levels were 650% higher (P < 0.003) and pituitary homogenate PRL mRNA levels were slightly increased (P < 0.04) in ovariectomized old us. mature rats. Neither serum LH values (P > 0.07) nor pituitary homogenate LH/3 mRNA levels (P > 0.1) differed in intact old and mature rats, whereas the corresponding medium concentrations of LH were reduced (P < 0.001). Ovariectomized old us. mature rats exhibited reductions in serum (P < 0.02) and medium (P < 0.001) LH concentrations, as well as in pituitary homogenate (P < 0.002) and cell lysate (P < 0.006) LH0 mRNA levels. Thus, these data revealed coordinate decreases with age in LH/3 mRNA and LH secretion, particularly in ovariectomized rats, suggesting an age-related alteration at or before LH/3 gene transcription. These findings parallel observations on other genes whose products change with age. In contrast, the observation that the increased secretion of PRL in old rats is accompanied by little or no increase in PRL mRNA is novel and suggests that age-related alterations in PRL gene expression proceed through a posttranscriptional mechanism.
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