Alessandro Mauri

Paraventricular nucleus lesion prevents yawning and penile erection induced by apomorphine and oxytocin but not by ACTH in rats.

The effect of electrolytic lesion of the paraventricular nucleus of the hypothalamus (PVN) on yawning and penile erection induced by apomorphine, oxytocin and adrenocorticotropic hormone (ACTH1-24) was studied in male rats. In sham-operated rats, apomorphine (50 micrograms/kg s.c.), oxytocin (30 ng i.c.v.), and ACTH1-24 (10 micrograms i.c.v.) significantly increased the number of yawning and penile erection episodes. In PVN-lesioned rats, apomorphine- and oxytocin-, but not ACTH-induced responses were strongly reduced. These results confirm our previous observations showing that the PVN has a crucial role in the expression of yawning and penile erection induced by dopamino-mimetic drugs and oxytocin, and suggest that ACTH-derived peptides induce the above responses by a mechanism not involving PVN hypothalamic dopamine or oxytocin.

Nitric oxide production is increased in the paraventricular nucleus of the hypothalamus of male rats during non‐contact penile erections and copulation

Male rats put in the presence of a receptive female rat that they can see, hear and smell, but cannot touch, show penile erection episodes. These non‐contact erections occur concomitantly with an increase in nitric oxide production in the paraventricular nucleus of the hypothalamus, as detected by the increase in the NO2– and NO3– concentration in the paraventricular dialysate obtained from these males by in vivo microdialysis.

Apomorphine- and Oxytocin-Induced Penile Erection and Yawning in Intact and Castrated Male Rats: Effect of Sexual Steroids

The effect of apomorphine (80 micrograms/kg s.c.) and oxytocin (30 ng i.c.v.) on penile erection and yawning was studied in intact and castrated male rats. In castrated rats both apomorphine and oxytocin responses were abolished. In these animals, testosterone (100 microgramS/kg s.c. once a day for 3 days), restored penile erection while estradiol benzoate (10 micrograms/kg s.c. once a day for 3 days) restored yawning induced by both compounds. 5-Dihydrotestosterone (DHT) or progesterone (each at a dose of 100 micrograms/kg s.c. once a day for 3 days) were ineffective. Given together, estradiol benzoate and DHT partially restored apomorphine- and oxytocin-induced yawning and penile erection, whereas estradiol benzoate and progesterone restored only yawning. Estradiol benzoate-induced recovery of yawning was prevented by the antiestrogen tamoxifen (1 mg/kg s.c. once a day for 3 days). In intact rats, progesterone increased and estradiol benzoate decreased apomorphine- and oxytocin-induced yawning without modifying penile erection, although oxytocin-induced yawning was prevented much less by estradiol benzoate than that induced by apomorphine. Testosterone or DHT were ineffective on both responses. Estradiol benzoate inhibition of apomorphine- and oxytocin-induced yawning was prevented by tamoxifen, which per se failed to modify apomorphine and oxytocin responses, as well as by testosterone or progesterone. The present results suggest that apomorphine- and oxytocin-induced penile erection and yawning are endocrine-dependent and differentially modulated by sexual steroids, suggesting that the mechanisms controlling the two behaviors are different even though they are often associated.

Obstetric and perinatal outcome in human immunodeficiency virus-infected pregnant women with and without opiate addiction.

This study was undertaken to assess the impact on gestation played by the simple human immunodeficiency virus (HIV)-seropositive status either alone or complicated by opiate abuse in the absence of other confounding variables. To this purpose the main obstetric complications and the perinatal outcome were prospectively evaluated in 38 simple HIV-infected women, 14 of whom were simple carriers and 24 under methadone treatment, and in 76 uninfected women, 16 of whom were methadone users and 60 controls. In simple HIV-carriers maternal weight gain (P < 0.001) and both 1- and 5-min Apgar scores (P < 0.005) were reduced whereas the incidence of miscarriage was increased (P < 0.05). Worse obstetric and perinatal outcomes were found in HIV-seropositive drug addicts, in which gestational length (P < 0.001), maternal weight gain (P < 0.001) and Apgar scores were lower (P < 0.005 and P < 0.001, respectively) and the rate of preterm labour, small for gestational age newborns, vaginal and urinary infections as well as of unexplained fever (P < 0.05) was higher. Outcomes were similar in HIV-seropositive and seronegative drug addicts and in both groups a positive correlation (r = 0.62 P < 0.001, and r = 0.44, respectively) was found between the number of infectious episodes throughout pregnancy and the mean dose of opiate consumed daily. Our results suggest that HIV-seropositive condition might exert slight direct and indirect detrimental effects on pregnancy. Whatever the maternal serologic status, opiate intake not only causes a further worsening of gestational and perinatal outcomes, but also increases the susceptibility towards pathogens.

Hypothalamic modulation of immunoreactive oxytocin in the rat thymus

Immunoreactive oxytocin was determined in a peptidic extract of rat thymus by means of a highly specific radioimmunoassay combined with high pressure liquid chromatography fractionation. Rat thymus was found to contain 80 +/- 7.5 pg/g wet tissue (congruent to 0.56 pg/mg protein) of oxytocin-like immunoreactivity, which behaved like synthetic oxytocin in the radioimmunoassay and in two different high pressure liquid chromatography columns. Oxytocin concentration was increased by bilateral electrolytic lesion of the paraventricular nucleus of the hypothalamus (PVN), and by high doses of corticosterone (10 mg/kg IM for 7 days) but was not modified by low doses of corticosterone (1 mg/kg IM for 7 days) or by hypophysectomy. The results suggest that rat thymus synthesizes oxytocin and that thymic oxytocin concentration is modulated by the hypothalamus.

Opposite changes in the content of oxytocin- and vasopressin-like immunoreactive peptides in the rat thymus during aging.

The content of oxytocin- and vasopressin-like immunoreactive (IR) peptides was measured in the thymic extract of 2, 5, 10, 15 and 20 month-old rats by radioimmunoassay before or after fractionation by high-pressure liquid chromatography. In both cases the content of the oxytocin-like IR peptide, which behaved like authentic oxytocin in the chromatography column, increased during aging. Compared to 2 month-old rats a significant 30% increase was observed in 5 month-old rats, whereas the maximal increase (200%) was found in 20 month-old rats. In contrast, the content of the vasopressin-like IR peptide, which behaved like authentic arg8-vasopressin in the chromatography column, decreased during aging. The decrease (30%) was evident in 5 month-old rats, and was maximal (80%) in 15 month-old rats. The present results suggest that the mechanisms regulating the content of oxytocin- and vasopressin-like IR peptides in the rat thymus undergo differential changes during aging. These processes might be linked to thymic involution.

Release of arachidonic acid metabolites by human fetal membranes: Interrelationship between leukotriene B4 and prostaglandin E2

The objective of this study was to ascertain whether human fetal membranes metabolize arachidonic acid preferentially through the lipoxygenase rather than the cyclooxygenase pathway before labor and whether an interaction between lipoxygenase and cyclooxygenase products is present in these tissues. Reflected fetal membranes were obtained from 8 healthy women at term gestation who were delivered by elective repeat cesarean section before the onset of labor. Tissues were cultured either in the presence or in the absence of the calcium ionophore A23187 for 60 minutes. Leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) were measured in culture medium by radioimmunoassays. Moreover, the effect of different concentrations of exogenously added LTB4 on PGE2 release was evaluated. The basal and stimulated output of LTB4 by tissues was significantly higher than that of PGE2. Addition of LTB4 significantly decreased PGE2 release by tissues. These findings suggest that in the above tissues: 1) the arachidonate lipoxygenase pathway is highly active before labor; 2) LTB4 might play a role in the regulation of PGE2 production.

Monosodium glutamate does not alter ACTH- or apomorphine-induced penile erection and yawning

The effect of the intracerebroventricular (ICV) injection of ACTH 1-24 (1, 5 and 10 micrograms) or the subcutaneous administration of apomorphine (20 and 80 micrograms/kg SC) on spontaneous penile erection and yawning was studied in rats treated with monosodium glutamate (MSG), a treatment that depletes hypothalamic ACTH, alpha-MSH and endorphin-like peptides. Neonatal MSG treatment failed to antagonize either apomorphine- or ACTH-induced yawning in male and female rats, or to alter the number of penile erection episodes induced by the two substances in male rats. In contrast, hypophysectomy, that does not alter the concentration of hypothalamic ACTH and alpha-MSH, caused a marked prevention of apomorphine- and ACTH-induced responses, in agreement with previous studies. The results suggest that the integrity of opiomelanotropinergic neurons in the hypothalamus is not necessary for the induction of yawning and penile erection by ACTH-derived peptides, and that apomorphine and other dopamine agonists apparently do not induce penile erection and yawning by releasing an ACTH-derived peptide in brain.

Plasma Alpha-Melanocyte-Stimulating Hormone during the Menstrual Cycle in Women

alpha-Melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropin (ACTH) immunoreactivity (IR) was measured in the blood of 22 healthy women with normal ovulatory process in the early and late follicular (near to ovulation) phases and in the early luteal phase of the menstrual cycle. Plasma alpha-MSH IR ranged from undetectable values to 81.3 pg/ml, the highest levels being found in the late follicular phase (15.52 +/- 4.16 pg/ml). In contrast, plasma ACTH IR was always detectable (range: 18.5-63.2 pg/ml), but its concentration did not differ significantly between the 3 phases of the menstrual cycle. High-pressure liquid chromatography fractionation of Sep pak C18-purified alpha-MSH IR revealed in all 3 phases the presence of 3 major peaks of alpha-MSH IR, coeluting with desacetyl-alpha-MSH, alpha-MSH and diacetyl-alpha-MSH, respectively. The most abundant peak always coeluted with authentic desacetyl-alpha-MSH, and the ratio between this deacetylated and the other 2 acetylated forms was similar in the 2 follicular phases (1:1.25 and 1:1.16 in the early and late phase, respectively), but significantly different in the luteal phase (1:0.48). The fluctuations in plasma concentration of the above MSH-related peptides suggest that different rates of alpha-MSH acetylation and release take place in the pituitary gland depending on the phase of the menstrual cycle.

Melanocortins and opioids modulate early postnatal growth in rats

This study was undertaken to investigate the effects of melanocortins and opioids on rat early postnatal body and organ growth. Among melanocortins tested desacetyl-alpha-melanocyte-stimulating hormone (alpha-MSH) at dosages of 0.3 and 3 micrograms/g/day was effective in stimulating neonatal growth with a weight gain of 7 and 5.6%, respectively, after 2 weeks of treatment. Likewise, a weight rise of 4.2 and 3% was obtained with 3 micrograms/g/day of both alpha-MSH and Nle4-D-Phe7 alpha-MSH. As far as opioids were concerned, while N-acetyl-beta-endorphin (beta-End) was ineffective, the activity of beta-End was dependent on dosage. Indeed, newborns treated with 0.03 microgram/g/day showed a slight, but significant, increase in weight, whereas a marked decrease in growth followed treatment with 0.3 and, mainly, 3 micrograms/g/day, with a final weight loss of 3.4 and 5.5%, respectively. All melanocortins exerted a positive action on muscular and brain trophism and, in addition, desacetyl-alpha-MSH also induced a rise of fat deposits. On the contrary, while the 0.03 microgram/g/day beta-End dose caused an increase in muscular and brain weight, the higher dosages of the opioid were detrimental, not only for muscle and brain, but also for both liver and spleen weight. A slight, although significant (P < 0.05), enhancement of serum dehydroepiandrosterone sulfate (DHEAS) level was found after the injection of 0.3 microgram/g desacetyl-alpha-MSH, whereas both the 0.3 and 3 micrograms/g doses of desacetyl-alpha-MSH and the 3 micrograms/g dose of alpha-MSH determined the rise of plasma androstenedione (P < 0.05). All tested melanocortins and opioids failed to modify the concentrations of corticosterone. Our results suggest that melanocortins and opioids can modulate early postnatal growth in rats either by direct or indirect mechanisms.