TY - JOUR
T1 - Mechanisms subserving the physiological nocturnal relative hypoprolactinemia of healthy older men
T2 - Dual decline in prolactin secretory burst mass and basal release with preservation of pulse duration, frequency, and interpulse interval - A general clinical research center study
AU - Iranmanesh, A.
AU - Mulligan, T.
AU - Veldhuis, J. D.
PY - 1999
Y1 - 1999
N2 - 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 21-34 yr) and 8 older (aged 62-72 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/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 band 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.
AB - 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 21-34 yr) and 8 older (aged 62-72 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/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 band 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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U2 - 10.1210/jcem.84.3.5514
DO - 10.1210/jcem.84.3.5514
M3 - Article
C2 - 10084599
AN - SCOPUS:0033029972
SN - 0021-972X
VL - 84
SP - 1083
EP - 1090
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 3
ER -