P. Chiodera

Relationship between plasma profiles of oxytocin and adrenocorticotropic hormone during suckling or breast stimulation in women

Oxytocin (OT) administration has been shown to inhibit adrenocorticotropic hormone (ACTH)/cortisol secretion in several experimental conditions. In the present study, the plasma OT responses to suckling in 7 lactating women or to mechanical breast stimulation in 6 normally menstruating women (experimental tests) or to sham stimuli in the same subjects (control tests) were measured and correlated with the simultaneous changes in plasma ACTH/cortisol levels. All women showed similar basal levels of OT, ACTH and cortisol, which remained unmodified after sham stimulation. In contrast, both suckling and breast stimulation produced a significant increase in plasma OT levels and a significant decrease in plasma ACTH concentrations. When OT and ACTH data were considered together, a significant negative correlation was found between the OT increase and the simultaneous ACTH decline. Plasma cortisol levels were lower during suckling or breast stimulation than in control conditions. These data show an inverse relationship between plasma OT and ACTH levels during suckling and breast stimulation in humans, suggesting an inhibitory influence of OT on ACTH/cortisol secretion in a physiological condition.

Inhibitory Action of Exogenous Oxytocin on Plasma Cortisol in Normal Human Subjects: Evidence of Action at the Adrenal Level

In previous studies we demonstrated that exogenous oxytocin induces a decrease of basal and stimulated cortisol and ACTH plasma levels in the normal male. To rule out the possibility that oxytocin could also act at the adrenal level, we tested, in the present work, the influence of exogenous oxytocin on the cortisol increase secondary to the intravenous injection of a supraphysiological dose (0.25 mg) of synthetic ACTH1-24 (Synachten) in 9 normal male volunteers. We demonstrate that oxytocin infusion does not modify the ACTH plasma levels but, however, induces a decreased cortisol response to ACTH1-24. These results support the hypothesis that, beside its hypophysial inhibitory action on ACTH release, oxytocin acts also at the adrenal gland level to decrease cortisol release and/or synthesis in normal human subjects.

Effects of Intravenously Infused Pituitary Adenylate Cyclase-Activating Polypeptide on Adenohypophyseal Hormone Secretion in Normal Men

The possible stimulatory effects of an intravenous infusion of increasing amounts of pituitary adenylate cyclase-activating polypeptide (PACAP) on anterior pituitary hormone secretions were evaluated in humans. Successively increasing doses of PACAP-38 (2, 4 and 8 pmol.kg-1.min-1; each dose for 20 min) were infused i.v. in 7 normal male subjects. On a different occasion, the same subjects were tested with vasoactive intestinal peptide (VIP; 4 pmol.kg-1.min-1 for 60 min). Circulating GH, ACTH, PRL, TSH and gonadotropin concentrations were measured before PACAP infusion and every 20 min, just before increasing the infusion dose of PACAP. Blood samples were taken before and every 15 min after the beginning of VIP administration. Serum levels of GH, TSH and gonadotropins did not change during PACAP or VIP infusion. Circulating ACTH and PRL concentrations were not modified by the infusion of the lowest dose of PACAP, whereas they were significantly increased in a dose-response fashion when higher amounts of PACAP were given. PRL, but not ACTH levels were significantly increased by VIP infusion. These data show for the first time in humans that ACTH and PRL secretions from the anterior pituitary gland are stimulated by the systemic administration of PACAP. In addition, since VIP stimulated only PRL secretion, PACAP-induced ACTH release appears to be mediated by specific receptors.

Simultaneous radioimmunoassay for plasma arginine-vasopressin and oxytocin using DEAE Sephadex A 25 extraction

A sensitive and specific radioimmunoassay method for simultaneous measurement of plasma arginine vasopressin (AVP) and oxytocin (OT) has been developed utilizing an extraction technique on DEAE Sephadex A 25. This procedure resulted in mean recoveries of 70.7% (AVP) and 65.4% (OT) in the peptide range of 5 to 100 pg/4 ml. The sensitivity of the assay is 0.5 pg/tube for AVP and 2 pg/tube for OT. The lower limit of detection for plasma extracts was 1.2 pg AVP/ml and 5 pg OT/ml plasma. Employing this method in normal human non smokers and ad libitum fluid the basal levels (mean ± SE) of plasma AVP are 3.5 ± 0.2 pg/ml in males and 4.6 ± 0.4 pg/ml in females and the basal concentrations of plasma OT are 5.1 ± 0.3 pg/ml in males and 5.4 ± 0.3 pg/ml in females. Dehydration and water loading produced significant changes in plasma AVP and OT concentrations and a significant correlation exists between plasma AVP and plasma (r= 0.96, p < 0.001 ) and urinary (r = 0.84, p < 0.01 ) osmolality, but not between plasma OT concentrations and plasma (r =0.11, NS) and urinary (r = 0.27, NS) osmolality. These results suggest that a wide range of physiological and pathophysiological changes in plasma AVP and OT can be simultaneously measured by the extraction procedure and the radioimmunoassay described.

Abnormal effect of cigarette smoking on pituitary hormone secretions in insulin‐dependent diabetes mellitus

OBJECTIVE We observed the effect of smoking two cigarettes on GH, AVP and cortisol secretion in patients with diabetes and normal subjects.

Beta-endorphin, adrenocorticotropic hormone and cortisol secretion in abstinent alcoholics

The circadian secretion of beta-endorphin, adrenocorticotropic hormone (ACTH), and cortisol was evaluated in 14 non-cirrhotic alcoholic men after 7 and 28 days of abstinence and in 12 sex- and age-matched normal subjects. A significant decrease in plasma levels of beta-endorphin, reduced ACTH levels, and increased cortisol levels were observed in samples taken at 08.00 h, 12.00 h, 18.00 h, and 23.00 h both after 7 and 28 days of abstinence. These data suggest the presence of a strong negative feedback on pro-opiomelanocortin synthesis by cortisol hypersecretion in abstinent alcoholics, which might be due to long-term stimulation of adrenal function by alcohol. The decreased plasma beta-endorphin levels might predispose to relapse in alcohol abuse.

Effect of estrogen or insulin-induced hypoglycemia on plasma oxytocin levels in bulimia and anorexia nervosa.

Plasma oxytocin (OT) levels were measured before and after stimulation with estrogens (1 mg ethynylestradiol orally) or with insulin (0.15 IU/kg)-induced hypoglycemia in seven underweight women with anorexia nervosa, eight normal weight bulimic women, and nine normal controls. Anorectic patients were amenorrhoic; they were tested at their first hospitalization (first tests) and again 8 to 9 weeks later (second tests) when they were eating normally, but were still at a low weight. In addition, anorectic women were tested 16 to 17 weeks after the first test (third tests), when their weight was restored to normal. Normal and bulimic women were tested on the fourth days of normal menstrual cycles. Insulin induced similar hypoglycemic responses in all groups. At each time point of the estrogen tests, plasma estrogen levels were similar in bulimic and normal women, whereas they were significantly lower in anorectic subjects. There were no differences in the basal levels of OT among groups. Both insulin-induced hypoglycemia and estrogen treatment produced striking OT increments in bulimic and control women, without significant differences between groups. During the first tests, no significant increase in plasma OT levels was observed in underweight anorectic women in response to both releasing stimuli. After partial weight recovery, the anorectic women showed a slight, but significant, increase in the OT responses to both insulin-induced hypoglycemia and estrogen administration. Both hypoglycemia- and estrogen-induced OT increases observed during the second tests were significantly lower in underweight anorectic patients than in normal controls. Anorectic subjects regained normal OT responsiveness to both stimuli after complete weight recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulation of ACTH/Cortisol by Intravenously Infused Substance P in Normal Men: Inhibition by Sodium Valproate

The effect of synthetic substance P (SP), infused intravenously in doses of 0.5, 1 or 1.5 pmol/kg-1/min-1 over 60 min on ACTH/cortisol secretion was evaluated in 7 healthy men. SP tests and a control test with normal saline were randomly performed at weekly intervals. During tests, SP infusion did not produce untoward side effects or changes in blood pressure. Plasma ACTH and cortisol levels were not modified when normal saline or the lowest dose of SP were infused, whereas they were significantly increased in a dose-dependent fashion when higher amounts of SP were administered. Further studies were performed in another 7 healthy men to test the possible influence of GABAergic neurotransmission on the ACTH/cortisol response to SP. For this purpose, subjects were tested with SP (1.5 pmol/kg-1/min-1) alone and on a different occasion with SP after pretreatment with the GABAergic agent sodium valproate (200 mg 16, 8 and 1 h before the SP test). Again, the administration of SP induced a significant increase in plasma ACTH and cortisol levels. The pretreatment with sodium valproate completely abolished both ACTH and cortisol responses to SP. These data demonstrate for the first time in humans that the systemic infusion of SP stimulates ACTH/cortisol secretion, suggesting the involvement of a GABAergic mechanism in the regulation of the action of SP.

Oxytocin response to insulin-induced hypoglycemia in obese subjects before and after weight loss.

The response of plasma oxytocin to an iv bolus injection of crystalline insulin (0.15 U/kg) was evaluated in 14 normal weight [mean body mass index (BMI) = 23] and in 9 obese (mean BMI = 42) men. Similar blood glucose decrements after insulin injection were observed in the two groups. Obese and normal weight subjects presented similar basal oxytocin levels. In both groups, oxytocin rose significantly during the insulin tolerance test (ITT); however, the peak oxytocin response in the obese men was significantly lower than in the normal weight subjects. Obese men were restudied after substantial weight loss. Basal oxytocin levels and glucose response to insulin did not change after weight reduction. The oxytocin response to the ITT was significantly higher than before slimming and did not differ from that observed in the normal weight subjects. A significant negative correlation between BMI values and oxytocin peak levels during ITT was observed in the lean controls and obese subjects (r = 0.516, p< 0.02). These results demonstrate that in obese subjects the oxytocin secretory response during an insulin tolerance test is reduced, suggesting the existence of a hypothalamic-pituitary disorder in obesity.

Specifically designed physical exercise programs improve children's motor abilities

Physical activity in schools is declining in many countries and inactivity in childhood has become a recognized risk factor. Data from a program of professionally guided physical exercise in primary school children were collected before and after the academic year of training. Four thousand five hundred children (6–10 years) were enrolled, and conditional and coordinative motor abilities (speed, trunk flexibility, long jumping, somersault, Harre circuit test) were measured. Anthropometric measurements were focused on body mass index (BMI), weight and height. Females never showed a significant variation of BMI, whereas males in the first and fourth grades showed significant differences. On the contrary, when considering the motor abilities studied, all the comparisons were highly significant. At the end of training, both males and females did better than at the beginning, and males were constantly faster than females. Our data, generated on a large number of children, show that professionally guided programs of physical education in the primary school lead to significant progresses in the development of conditional and coordinative abilities, without altering BMI values, thus not interfering with the balanced progression of body weight and height.