Effects of Gender on Neuroendocrine and Metabolic Counterregulatory Responses to Exercise in Normal Man

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Abstract
Significant, sexual dimorphisms exist in counterregulatory re- sponses to commonly occurring stresses, such as hypoglycemia, fast- ing, and cognitive testing. The question of whether counterregulatory responses differ during exercise in healthy men and women remains controversial. The aim of this study was to determine whether a sexual dimorphism exists in neuroendocrine, metabolic, or cardio- vascular responses to prolonged moderate exercise. Sixteen healthy (eight men and eight women) subjects matched for age (28 6 2 yr), body mass index (22 6 1 kg/m2), nutrient intake, and spectrum of physical fitness were studied in a randomized fashion during 90 min of exercise on a cycle ergometer at 80% of their anaerobic threshold (>50% VO2 max). Respiratory quotient and oxygen consumption rel- ative to body weight were identical in men and women. Glycemia was equated (5.3 6 0.2 mmol/L) during exercise via an exogenous glucose infusion. Gender had significant effects on counterregulatory re- sponses during exercise. Arterialized epinephrine (1.05 6 0.2 vs. 0.45 6 0.04 nmol/L), norepinephrine (9.2 6 1.1 vs. 5.8 6 1.1 nmol/L), and pancreatic polypeptide (52 6 6 vs. 37 6 6 pmol/L) were signifi- cantly (P , 0.01) increased in men compared to women, respectively. Plasma glucagon, cortisol, and GH levels responded similarly in men and women. Insulin values were higher at baseline in men and fell by a greater amount to reach similar levels during exercise compared to those in women. Endogenous glucose production, measured with (3-3H)glucose was similar in men and women. Carbohydrate oxidation was significantly increased in men relative to women (21.2 6 2 vs. 15.6 6 2 mg/kg fat free masszmin; P , 0.05). Despite reduced sym- pathetic nervous system (SNS) drive, lipolytic responses were in- creased in women. Arterialized blood glycerol (215 6 30 vs. 140 6 20 mmol/L), b-hydroxybutyrate (54 6 9 vs. 25 6 10 mmol/L), and plasma nonesterified fatty acids (720 6 56 vs. 469 6 103 mmol/L) were sig- nificantly (P , 0.01) increased in women. In keeping with increased SNS activity, systolic blood pressure and mean arterial pressure were significantly increased (P , 0.01) in men. In summary, this study demonstrates that a significant sexual dimorphism exists in neuroendocrine, metabolic, and cardiovascular counterregulatory responses to prolonged moderate exercise in man. We conclude that during exercise, men have increased autonomic nervous system (epinephrine, norepinephrine, pancreatic polypep- tide), cardiovascular (systolic, mean arterial pressure) and certain metabolic (carbohydrate oxidation) counterregulatory responses, but that women have increased lipolytic (glycerol, nonesterified fatty ac- ids) and ketogenic (b-hydroxybutyrate) responses. Women may com- pensate for diminished SNS activity during exercise by increased lipolytic responses. (J Clin Endocrinol Metab 85: 224 -230, 2000)

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