Adrenocorticotropic hormone (ACTH) levels were compared before and after submaximal and exhaustive isotonic exercise in six normally active college students (3 men and 3 women). Each subject participated in three experiments conducted at the same morning hour. Venous plasma was obtained before and immediately after 20-min runs at 65 and 80% of maximal O2 consumption (VO2 max) and after a run of gradually increasing work intensity which resulted in exhaustion (100% VO2 max) in 12.6 +/- 1.3 min. ACTH (mean +/- SE) was 48 +/- 15, 57 +/- 12, and 61 +/- 11 pg/ml before the 65, 80, and 100% VO2 max runs, and increased to 61 +/- 15 (NS), 128 +/- 18 (P less than 0.05), and 292 +/- 72 (P less than 0.05) pg/ml, respectively. Plasma glucose, growth hormone, cortisol, and lactic acid concentrations increased in a similar fashion. Cortisol and ACTH levels were significantly correlated at the higher levels of exertion: r = 0.18 (NS) for the 65% VO2 max run, r = 0.65 (P less than 0.05) for the 80% VO2 max run, and r = 0.64 (P less than 0.05) for the run to exhaustion. Both the change in ACTH with exercise and its postrun concentration were significantly related to the change in plasma lactic acid (r = 0.65, P less than 0.05) and the postrun plasma lactic acid (r = 0.64, P less than 0.05). We conclude that exercise-induced increases in plasma ACTH and their correlation with circulating cortisol depend on the intensity of isotonic exercise. Our observations also suggest that plasma lactic acid may influence ACTH release during exercise.

Obese mice (C57BL/6J ob/ob) and their lean littermates were studied at various ages from immediately post weaning until 62 weeks of age, at which mortality increased markedly. Several age-related changes were noted. 1) Plasma glucose levels were elevated in obese mice 5-20 weeks and 62 weeks of age, but were similar to those in the lean mice at 20-60 weeks of age. Plasma insulin levels were elevated in obese mice, and there were no age-related differences. 2) Brain serotonin was elevated in obese mice at all ages and increased with age in both obese and lean animals. 3) Pituitary contents of ACTH and beta-endorphin were elevated in young obese mice and increased further as these mice approached their life expectancy. 4) The ratios of ACTH to beta-endorphin immunoreactivities were similar in obese and lean mice, except in obese mice over 50 weeks of age where this ratio was increased. We conclude that: 1) the obese mouse is characterized by hyperinsulinemia and hyperadrenocorticism throughout its life; 2) the insulin resistance of the obese mouse improves at 20 weeks of age, yet deteriorates as its life expectancy is approached; 3) the obese mouse has an elevated brain serotonin content similar to previously described elevations of the putative neurotransmitters dopamine and norepinephrine in these mice; and 4) as the obese mouse approaches its life expectancy, abnormalities may occur in the synthesis, processing, or secretion of ACTH and/or beta-endorphine.

Vasoactive intestinal polypeptide (VIP) has been identified in hypothalamic tissue, is secreted into hypophysial portal blood, and stimulates prolactin (PRL) release in vivo and in vitro. It has been proposed, therefore, that VIP is a physiologic PRL-releasing factor. In this study, we confirm that VIP stimulates PRL release from rat pituitary cells in vitro, and demonstrate that an anti-VIP antiserum blocks VIP-induced PRL secretion. Surprisingly, the anti-VIP antiserum inhibited basal PRL secretion from rat pituitary cells in 3 separate experiments. Data from these experiments were pooled, as the responses were similar, revealing basal PRL release of 10.7 + 1.3 ng rPRL/10⁵ cells (X ± SE), while anti-VIP antisera significantly inhibited release to 4.4 ±0.6 ng rPRL/10⁵ cells (p < 0.001). PRL release in incubates containing control non-immune sera did not differ from basal release, 8.1 ng rPRL/10⁵ cells. A further control experiment was conducted wherein cells were incubated with an anti-ACTH antiserum, representing another hyperimmune serum, which had no effect on PRL secretion. These data suggest that VIP, in addition to its possible role as a hypothalamic-derived PRL-releasing factor, may play a role within the pituitary as a regulator of basal PRL secretion.

Previous studies have suggested that vasoactive intestinal polypeptide (VIP) is involved in regulation of PRL secretion within the pituitary gland. In order to determine whether VIP is synthesized in anterior pituitary tissue, we performed three experiments. In all experiments, anterior pituitaries were obtained from male rats. The tissue was then labeled by incubation in leucine-free minimum essential medium containing [3H]leucine, 14 microCi/ml. In Exp I, the labeled tissue was homogenized, centrifuged, and the supernatant was chromatographed on Sephadex G-50F. The fractions indicated a large peak of counts near the void volume and another peak coeluting with VIP. These latter fractions were pooled and subjected to reverse phase HPLC. Fractions from the HPLC indicated: a protein peak, VIP immunoreactivity, and maximum counts immunoprecipitated by anti-VIP serum at the retention time of synthetic porcine VIP. Exp II consisted of perifusion of labeled pituitary quarters over a 120-min period followed by an additional 60 min in the presence of 56 mM KCl. During this latter period of KCl depolarization, a large amount of 3H-labeled material was secreted. These fractions were then chromatographed on Sephadex G-50F, and the fractions coeluting with [125I]porcine VIP were subjected to immunoprecipitation with anti-VIP serum. In addition, all fractions from the Sephadex column were assayed for VIP, and the only activity was at the elution volume of [125I]porcine VIP. In Exp III, the pituitary labeling procedure included 3.6 X 10(-5) M cycloheximide. Subsequently, the tissue was perifused and the perifusate collected during the 60-min 56 mM KCl perifusion phase was pooled and immunoprecipitated with anti-VIP serum. No immunoprecipitable counts were obtained. These experiments indicate that anterior pituitary tissue synthesizes VIP on the basis of the HPLC profile and immunoprecipitation with specific anti-VIP antiserum. These results, in addition to other studies by our laboratory and others, suggest that intrapituitary VIP may be an important regulator of anterior pituitary hormone secretion, particularly PRL.

In vitro 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] production in kidney slices from normal intact rats averaged 16 +/- 4 pmol/g . h and was increased about 8-fold by phosphate deprivation and 5-fold by calcium deprivation to levels averaging 128 +/- 12 and 84 +/- 19 pmol/g x h, respectively. Hypophysectomy in phosphate-deprived rats completely abolished any increase in 1 alpha-hydroxylase activity, while calcium deprivation in hypophysectomized (hypox) rats resulted in a 4-fold increase in 1 alpha-hydroxylase activity. Replacement of hypox rats fed a low phosphorus diet with pituitary extracts resulted in a 4-fold stimulation of 1 alpha-hydroxylase activity in response to the hypophosphatemic stimulus. However, replacement of hypox rats fed a normal phosphorus diet with pituitary extract stimulated 1 alpha-hydroxylase activity only 2-fold. Replacement of hypox rats fed a low phosphorus diet with GH resulted in a 3.5-fold elevation in plasma 1,25-(OH)2D3 levels, while no such elevation in plasma 1,25-(OH)2D3 levels was observed in similarly treated animals replaced with PRL, ACTH, TSH, or T3. Replacement of hypox rats eating a normal diet with GH resulted in no significant change in plasma 1,25-(OH)2D3 levels. These results suggest that GH is required for maintenance of elevated plasma 1,25-(OH)2D3 levels during dietary phosphate deprivation and that this effect is mediated by increased renal 1,25-(OH)2D3 synthesis.