The effect of testosterone (T) replacement on changes in mood was studied for 60 days in 51 hypogonadal men. All patients were withdrawn from their prior T replacement for at least 6 weeks before enrollment. Of these patients, 18 received T enanthate 200 mg im every 20 days, 16 received sublingual T cyclodextrin (SLT) at a dose of 2.5 mg three times daily, and 17 received SLT at a dose of 5.0 mg three times daily. The total treatment period was 60 days. The patients were asked to respond to a questionnaire on 7 consecutive days before the start of treatment and on 7 consecutive days before their visits to the clinic on days 21, 41, and 60 of treatment. The following mood parameters were assessed using a 7-point Likert rating scale: angry, alert, irritable, full of pep (energy), sad/blue, tired, friendly, nervous, and well/good. When compared with the baseline period, T replacement led to significant decreases in anger (P = 0.0045), irritability (P = 0.0009), sadness (P = 0.0033), tiredness (P = 0.0035), and nervousness (P = 0.0291), and significant improvement in energy level (P = 0.0020), friendliness (P = 0.0072), and sense of well-being (P = 0.024) in all subjects as a group. Analyses of the area under the curve (AUC) of baseline serum T levels before T replacement showed significant positive correlations between serum T (AUC) and friendliness (r = 0.29, P < 0.05) and sense of well-being (r = 0.27, P < 0.05), and significant negative correlations with nervousness (r = -0.27, P < 0.05), irritability (r = -0.29, P < 0.05) and tiredness (r = -0.28, P < 0.05). Similar correlations were found between serum dihydrotestosterone (DHT) and some of the mood parameters. After T replacement in the hypogonadal men, these correlations between AUC of serum T levels and the positive and negative mood scores disappeared. These results were corroborated in a subsequent study in which 30 hypogonadal men were supplemented with SLT 5 mg three times daily for 6 months. The patients were less nervous (P = 0.0025) and more alert (P = 0.0004), friendly (P = 0.042), and energetic (P = 0.0001) during the 6-month treatment period compared with baseline. We conclude that T replacement therapy in hypogonadal men improved their positive mood parameters, such as energy, well/good feelings, and friendliness and decreased negative mood parameters including anger, nervousness, and irritability, and direct correlations between serum T and DHT with mood scores were only observed in the baseline period when serum androgen levels were below the normal range. The latter observation suggests that once a minimally adequate serum T/DHT level was achieved by T replacement therapy, further increases in serum T/DHT levels did not further contribute to the improvement in mood variables.

No abstract

To clarify the source of human urine EGF, we studied EGF renal clearance in 20 healthy, young adult subjects. Immunoreactive EGF was measured hourly in EDTA plasma, heparin plasma, serum and urine of 12 males and 8 females during a 3 h study period. Plasma and urine creatinine and creatinine clearance were measured and calculated hourly. Mean (and SEM) creatinine clearance was similar in males and females (118 +/- 12 vs 105 +/- 6 ml/min). EGF was not detectable in plasma, whereas relatively high levels were measured in serum (2.5 +/- 0.25 vs 1.5 +/- 0.18 ng/ml in males and females respectively p less than 0.05). Urine EGF excretion averaged 1641 +/- 233 ng/h in males and 1507 +/- 191 ng/h in females (p greater than 0.05). A significant correlation was observed between urine creatinine and urine EGF concentrations in both male (r = 0.98, p less than 0.01) and female (r = 0.94, p less than 0.01) subjects. EGF immunoreactivity in urine and serum eluted from G-75 sephadex columns similarly to recombinant 6000 Mr hEGF. Urine excretion of EGF approximated 1.5 micrograms/h or 25 ng/mg creatine. The high concentrations of EGF found in urine in the face of non-detectable levels of EGF in plasma favor the hypothesis that EGF in urine is derived from kidney synthesis and secretion. The significant positive correlation between urine creatinine and urine EGF suggests a functional correlation between glomerular filtration and the process of tubular EGF excretion.

ABSTRACT. A marked increase in plasma catecholamines at birth has been described in animals and man. Because the factors that regulate catecholamine secretion are incompletely understood and because it has recently been suggested-that endogenous opiates are important in the regulation of catecholamine secretion, we designed studies to2etermine the influence of opiate receptor blockade prior to delivery on the increase in plasma catecholamines at birth. Term fetal sheep were delivered by cesarean section and randomly assigned to receive naloxone or vehicle. Naloxone was given just prior to umbilical cord cutting as a 2 mg/kg bolus followed by 2 mg/kg/h. Naloxone administration resulted in significantly greater peak levels of plasma norepinephrine (peak levels of 1.5 f 0.4 versus 0.9 f 0.1 ng/ml) and epinephrine (peak levels of 1.4 f 0.7 versus 0.9 f 0.3 ng/ml) and higher norepinephrine values throughout the study period. Naloxone administration was associated with significantly elevated heart rate (peak 184 f 12 versus 207 f 13 beats per min) and blood pressure (peak 95 f 6 versus 88 f 2 mm Hg). These studies demonstrate that opiate receptor blockade from birth markedly augments the neonatal sympathoadrenal response in the term newborn lamb. Fetal and newborn animals secrete catecholamines in response to a variety of stimuli including hypoxia (I), hemorrhage (2), hypothermia (3), labor (4), and delivery (5). The marked increase in catecholamine secretion at birth is particularly important because of the wide range of physiological changes which occur at birth and the importance of the sympathoadrenal system in modulating these changes. In the chronically catheterized fetal sheep, plasma catecholamines begin to rise in the last 3 h of Received September 30, 1986; accepted January 9, 1987 spontaneous labor prior to delivery (4). There is then a further augmentation in plasma levels of both NE and E following delivery and cord cutting (6). We were interested to extend our observations to study the factors that regulate catecholamine release at birth.Two levels of control of catecholamine release have been recognized, including oc 2 receptor-mediated presynaptic inhibition of NE release and inhibition by endogenous opiate peptides. BEND is secreted in response to stress (7) and degrees of hypoxia in fetal sheep known to produce marked catecholamine secretion result in markedly increased levels of circulating BEND (8).Catecholamines and ENK are costored and secreted by the adrenal medulla in response to cholinergic or splanchnic nerve stimulation (9-12). Opiate peptides inhibit catecholamine release by inhibition of neurotransmission in sympathetic ganglia (13,14) and inhibition of adrenal medullary catecholamine secretion (1 5). The physiological significance of these observations in vivo is unclear. In the present study, in order to investigate the role of endogenous opiates in vivo as modulators of sympathoadrenal activity at birth, we compared plasma catecholamine levels with and without continuous opiate receptor...