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From the Clinical Research Centers |
Endocrine Section, Medical Service, Salem Veterans Affairs Medical Center (A.I.), Salem, Virginia 24153; Geriatrics Medicine, Hunter Holmes McGuire Veterans Affairs Medical Center (T.M.), Richmond, Virginia 23249; and the Division of Endocrinology, Department of Internal Medicine, National Science Foundation Center for Biological Timing, University of Virginia Health Sciences Center (J.D.V.), Charlottesville, Virginia 22908
Address all correspondence and requests for reprints to: Dr. Johannes D. Veldhuis, Division of Endocrinology, Department of Internal Medicine, Box 202, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908. E-mail: jdv{at}virginia.edu
Increasing age is accompanied by decrements in randomly obtained, fasting, or frequently sampled serum PRL concentrations. The precise neuroendocrine mechanisms underlying such relative hypoprolactinemia in aging are incompletely understood. In the present study, we sampled blood at 2.5-min intervals overnight in 11 young (aged 2134 yr) and 8 older (aged 6272 yr) healthy men for subsequent chemiluminescence-based assay of serum PRL concentrations. The mean (±SEM) serum PRL concentration was significantly reduced at 4.3 ± 0.78 µg/L in older men compared with 9.5 ± 1.2 µg/L in young volunteers (P = 0.0049). PRL concentrations correlated with serum testosterone (r = 0.473; P = 0.041), dehydroepiandrosteroen sulfate (r = + 0.455, P = 0.05), and insulin-like growth factor I (r = 0.494; P = 0.032) levels. Deconvolution analysis was used to evaluate combined pulsatile and basal modes of PRL secretion. In older men, discrete PRL secretory bursts were marked by a significantly (2.4-fold) attenuated mass of hormone secreted per burst (amount of PRL secreted per unit distribution volume), viz. 1.6 ± 0.23 (older) vs. 3.9 ± 0.57 µg/L (young; P < 0.01). In contrast, PRL secretory burst frequency, interpulse interval, and pulse duration were invariant of age. Concomitantly, basal PRL secretion was reduced by 2-fold in older subjects, namely to 0.00030 ± 0.00027 (older) vs. 0.00065 ± 0.0002 µg/L/min (young; P < 0.01). The amount of total PRL secretion that was pulsatile averaged 82 ± 5.3% in young and 99 ± 0.13% in older men (P = 0.012), indicating preferential loss of the basal mode of PRL release in aging.
Assuming that basal PRL secretion mirrors functional pituitary lactotroph cell secretory mass, whereas pulsatile PRL release reflects effective (net) intermittent hypothalamic drive to responsive lactotroph cells, then our results suggest both an attrition in lactotroph cell mass and an impoverishment of net positive hypothalamic (agonistic) input to lactotrophs in older men. Given the multiple roles of PRL reported in experimental animals (e.g. on the one hand to support immune function and adrenal androgen biosynthesis and on the other hand to activate intraprostatic growth factors), we suggest that the nocturnal relative hypoprolactinemia observed in healthy aging men may have both adaptive and maladaptive clinical implications to target tissues.
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