A. Cagnacci

Modulation of anterior pituitary luteinizing hormone response to gonadotropin-releasing hormone by insulin-like growth factor I in vitro.

OBJECTIVE To investigate how much insulin-like growth factor I may modulate the LH response to GnRH. DESIGN In primary cultures of male rat anterior pituitary cells, the LH response to GnRH (10(-9) M) was evaluated after a 24-hour preincubation with medium alone, IGF-I (1, 5, 10, 15 nM), polyclonal antibody anti-IGF-I (Ab-anti-IGF-I), (1:3,000; 1:10,000), or rabbit serum (1:3,000; 1:10,000) as control. MAIN OUTCOME MEASURE Gonadotropin-releasing hormone-induced LH release from primary cultures of male rat anterior pituitary cells. RESULTS Insulin-like growth factor I induces a dose-dependent stimulus on the LH response to GnRH. Insulin-like growth factor I at doses of 10 and 15 nM exerted a maximal stimulus, increasing the LH response to GnRH by 30%. The Ab-anti-IGF-I at both dilutions reduced the LH response to GnRH by 30%. No effect was exerted by rabbit serum. CONCLUSIONS Present data indicate that IGF-I may enhance the normal LH response to GnRH from rat anterior pituitary glands, suggesting important influences of this growth factor in the modulation of anterior pituitary LH release.

Melatonin-induced decrease of body temperature in women:A threshold event.

Whether the biological effect of melatonin in humans is directly related to the circulating levels of the hormone, has not heretofore been investigated. In this study, we investigated whether previously described hypothermic melatonin properties are dose related. The nocturnal decline of the body temperature (BT) observed in 16 early follicular phase women, following placebo administration at 18.00 h, was compared with that observed during the preceding or following night, after melatonin suppression with the beta 1-adrenergic antagonist atenolol (100 mg). In 6 subjects (37.5%) with lower nocturnal melatonin levels (p < 0.05) atenolol induced a complete melatonin suppression and an attenuation of the nocturnal BT decline (p < 0.02), whereas in the remaining 10 subjects (62.5%) atenolol induced an incomplete melatonin suppression with no modification of the nocturnal BT decline. During a 3rd night, 2 of the 6 subjects with complete and 6 of the 10 subjects with incomplete melatonin suppression blindly received atenolol plus melatonin (1 mg at 19.30 h and 0.75 mg at 21.00 and 23.00 h). Exogenous melatonin restored the full expression of the nocturnal BT decline in the 2 subjects with complete melatonin suppression, but did not modify the BT decline in the 6 subjects with atenolol-induced incomplete melatonin suppression. Our data show that markedly, but not completely attenuated nocturnal melatonin levels are sufficient to exert maximal thermoregulatory effects, indicating rather a threshold than a dose-response effect of melatonin action on human BT.

Melatonin enhances Cortisol levels in aged women: Reversible by estrogens

Cagnacci A, Soldani R, Yen SSC. Melatonin enhances Cortisol levels in aged women: Reversible by estrogens. J. Pineal Res. 1997; 22:81–85.

Exogenous melatonin enhances luteinizing hormone levels of women in the follicular but not in the luteal menstrual phase

OBJECTIVE To investigate the effect of exogenous melatonin on LH pulsatility in women during the follicular and luteal menstrual phases. DESIGN Randomized, double-blind placebo-controlled study. PATIENTS Normal cycling young women (25 to 35 years old). INTERVENTIONS Each subject was admitted at the Clinical Research Center for 2 consecutive days on both the follicular and the luteal menstrual phases. On each day, at 7:00 A.M. an indwelling catether was placed in an antecubital vein for a 10 minutes blood sampling from 9:00 A.M. to 5:00 P.M. On the 2 consecutive days of both the follicular and the luteal menstrual phases, each subject randomly received either placebo or melatonin pills (1 mg at 8:00 and 0.75 mg at 10:00 and 12:00 A.M.). MAIN OUTCOME MEASURE Luteinizing hormone pulsatility. RESULTS The amplitude of LH pulses and mean LH levels were increased by melatonin in the follicular but not in the luteal menstrual phase. CONCLUSIONS The stimulatory effect of exogenous melatonin on LH is modulated by the endocrine environment and selectively exerted in the follicular phase of the menstrual cycle.

Effect of sex steroids on body temperature in postmenopausal women. Role of endogenous opioids

The role of endogenous opioids on the thermoregulatory effect of sex steroids was investigated in six postmenopausal women before and during treatment with transdermal 17 B-estradiol (TTS 50; 50 mcg/day) with or without vaginal progesterone (P4; 100 mg twice daily). In all the different endocrine conditions, saline or the opioid antagonist naloxone (10 mg/hr. preceded by 10 mg iv bolus) were randomly infused for 4 hrs., on two consecutive days. Measurements of body temperature (BT) variations were performed by a thermistor probe placed in the rectum. BT did not significantly vary from baseline values during saline infusion, whereas it significantly decreased during the infusion of naloxone performed, either before treatment (p less than 0.01), during TTS 50 administration (p less than 0.01), or during TTS 50 + P4 (p less than 0.025). The naloxone induced decrease of BT was greater during TTS 50 administration than before treatment (p less than 0.025). The addition of P4 to TTS 50 administration increased baseline BT of 0.4 degrees C (p less than 0.01), and reduced the ability of naloxone to reduce BT (p less than 0.01 vs. TTS 50). The hyperthermic effect of P4 was not abolished by the infusion of naloxone. Our data show that in postmenopausal women the effect of endogenous opioid peptides on BT is enhanced by estradiol and reduced by progesterone. The hyperthermic effect of progesterone does not seem to be mediated by an increased endogenous opioid activity.