Biomedical subjects

M Gambacciani

Publications and source records attributed to M Gambacciani.

At least 73 records · Page 4Linked to original sources

PubMed1989

Regulation of body temperature in postmenopausal women: interactions between bromocriptine and the endogenous opioid system.

The role exerted by the endogenous opioid system on thermoregulation has been studied in nine postmenopausal women before and after the chronic administration of the dopamine agonist bromocriptine (5 mg/day). These women randomly received an infusion of the opioid antagonist naloxone (1.6 mg/h for 4 h) or saline on two consecutive days, before and after 30 days of bromocriptine administration. Body temperature as evaluated by rectal temperature, did not vary during saline infusion performed both before and after 30 days of bromocriptine administration. In untreated women naloxone infusion significantly reduced body core temperature. The hypothermic response to naloxone was significantly greater following chronic bromocriptine administration. These results indicate that bromocriptine seems to increase the activity of the endogenous opioid system on the mechanisms which regulate body temperature in postmenopausal women.

Body Temperature Regulation↗

PubMed1989

Reduction in the size of prolactin-producing pituitary tumor after Cabergoline administration.

Different weekly doses (400 to 3,000 micrograms) of the new, long-acting dopamine agonist Cabergoline (Farmitalia Carlo Erba, Milan, Italy) were given to 11 hyperprolactinemic women with pituitary tumor. Pituitary computerized tomography (CT) scans were performed before the start of treatment and after 3 (n = 5), 6 (n = 3), and 9 (n = 3) months of Cabergoline administration. Plasma prolactin (PRL) was determined in blood samples collected before and at weekly intervals during Cabergoline administration. Cabergoline induced marked inhibition of PRL secretion in conjunction with a CT demonstration of reduction in the pituitary tumor size in all patients. The potent, long-lasting PRL inhibitory effect of Cabergoline and the absence of side effects typical of dopaminergic compounds suggest that the use of this drug is advantageous over others in the medical treatment of hyperprolactinemia.

Adolescent↗

PubMed1989

Influence of oestradiol and progesterone on pulsatile LH secretion in postmenopausal women.

Pulsatile LH secretion was studied in six healthy postmenopausal women. Blood samples were obtained every 10 min during an 8-h saline infusion performed before and during the administration of transdermal oestradiol alone (E2; 50 micrograms/day) and in combination with vaginal progesterone (P; 100 mg twice daily). Plasma E2 and P levels reached values similar to those found in the early follicular phase and in the luteal phase of the menstrual cycle, respectively. The mean plasma LH levels significantly decreased (P less than 0.01) during transdermal E2 with and without vaginal P. A significant increase in the frequency (P less than 0.025) and the amplitude (P less than 0.05) of LH pulses was observed during transdermal E2. The administration of vaginal P to oestrongenized women significantly blunted the frequency (P less than 0.05) and enhanced the amplitude (P less than 0.05) of LH pulses. In all experimental conditions, the mean plasma LH levels showed a positive linear correlation with the amplitude of LH pulses. The present results show that peripheral levels of E2, similar to those of the early follicular phase of the menstrual cycle, can influence the pulsatile pattern of LH secretion, enhancing the frequency and the amplitude of LH pulses. In oestrogenized patients, the increase of peripheral P plasma levels to postovulatory values restored a pulsatile pattern of LH secretion similar to that of the early luteal phase of menstrual cycle.

Administration, Cutaneous↗

PubMed1989

Pulsatile gonadotropin-releasing hormone release from the human mediobasal hypothalamus in vitro: opiate receptor-mediated suppression.

An in vitro perifusion system was used to investigate pulsatile gonadotropin-releasing hormone (GnRH) release from the fetal (20-23 weeks of gestation) and adult human mediobasal hypothalamus (MBH). Fetal human MBHs released GnRH in discrete pulses, with a periodicity of approximately 1 h. Adult human MBHs also released GnRH in a pulsatile manner, with a periodicity of 60-100 min. The calcium-dependent pulsatile GnRH release from fetal human MBHs was suppressed by addition of morphine (10 microM) to the perifusion medium, and this suppression was reversed by addition of the opiate receptor antagonist naloxone (10 microM). These results indicate that the human hypothalamic GnRH pulse-generating mechanism is located entirely within the MBH, and that this pulse generator can maintain intrinsically pulsatile GnRH release independent of all innervation from outside this site. Our data also demonstrate that human hypothalamic pulsatile GnRH release can be suppressed by an opiate receptor-mediated mechanism located within the MBH.

Activity Cycles↗

PubMed1988

GnRH stimulates ACTH and immunoreactive beta-endorphin release from the rat pituitary in vitro.

An in vitro perifusion system was used to investigate the effects of GnRH stimulation on LH, ACTH, and immunoreactive beta-endorphin (i beta-END) release from ovariectomized (1 week) rat anterior hemipituitaries. Either 0, 8 or 80 nM GnRH was administered as a 15 min pulse followed 30 min later by a prolonged 45 min infusion. Both 8 and 80 nM GnRH induced comparable LH release in response to the 15 min as well as the 45 min GnRH stimulation. The initial 15 min exposure to either 8 or 80 nM GnRH did not induce significant changes in ACTH or i beta-END release. In contrast, the subsequent 45 min exposure to 8 nM GnRH induced a significant (p less than 0.01) increase in ACTH release, and the 45 min exposure to 80 nM GnRH induced a significant (p less than 0.01) increase in ACTH as well as i beta-END release. Equimolar (i.e. 8 or 80 nM) GnRH receptor antagonist (ANT) blocked the stimulatory effects of GnRH in all cases. These results demonstrate that GnRH can stimulate not only LH but also ACTH and i beta-END release from ovariectomized rat anterior hemipituitaries in vitro, apparently by a GnRH receptor mediated mechanism independent of actual LH release. Although the time course of these responses appears to be consistent with the hypothesis that GnRH-stimulated gonadotropes release paracrine factor(s) which stimulate corticotrope activity, the mechanism of these responses remains to be determined.

Adrenocorticotropic Hormone↗

PubMed1988

Chronic bromocriptine administration restores luteinizing hormone response to naloxone in postmenopausal women.

To evaluate whether dopaminergic treatment may modify endogenous opioid activity at the hypothalamic-pituitary level, the effects of naloxone infusion (1.6 mg/h for 4 h) on luteinizing hormone (LH) secretion were studied in 5 postmenopausal women either before or after chronic administration of the dopaminergic drug bromocriptine (BCT; 5 mg/day for 30 days). BCT administration did not modify mean plasma LH levels. Before treatment naloxone infusion did not induce any significant modification of LH secretion. Conversely, after chronic BCT administration naloxone induced a significant (p less than 0.05) increase in plasma LH levels. The LH response to naloxone was significantly (p less than 0.001) higher than that observed before BCT. The present data show that chronic BCT administration restores the LH response to naloxone in postmenopausal women. Therefore, these results seem to demonstrate that BCT administration can enhance opioid activity, suggesting an involvement of the endogenous opioid system in dopaminergic modulation of gonadotropin release.

Bromocriptine↗

PubMed1988

Restoration of luteinizing hormone response to naloxone in postmenopausal women by chronic administration of the antidopaminergic drug veralipride.

To determine whether antidopaminergic drug administration may modify endogenous opioid activity at the hypothalamic-pituitary level, the effects of naloxone infusion (1.6 mg/h for 4 h) on LH secretion were studied in six postmenopausal women before and after administration of the potent antidopaminergic drug veralipride for 20 days. Before veralipride administration, the naloxone infusion did not alter LH secretion. Chronic administration of veralipride resulted in a significant (P less than 0.01) decline in plasma LH levels. In addition, the naloxone infusion induced a significant (P less than 0.05) increase in plasma LH levels, which reached values similar to those before veralipride administration. These results demonstrate that in postmenopausal women the antidopaminergic drug veralipride can restore, at least in part, the activity of the endogenous opioid system. These findings suggest that endogenous opioid peptides may mediate the inhibitory effect exerted by chronic antidopaminergic drug administration on LH secretion in humans.

Adult↗

PubMed1988

Pulsatile beta-endorphin release from the human pituitary in vitro.

An in vitro perifusion system was used to characterize spontaneous immunoreactive beta-endorphin (i beta-END) release from 10 human fetal (20-23 weeks gestation) and 2 human adult anterior pituitaries. Spontaneous i beta-END release from fetal anterior pituitaries was pulsatile, with a mean (+/- SE) pulse interval of 9.1 +/- 0.5 minutes, pulse amplitude of 120.8 +/- 46.1 pg with nadir to peak increment of 106.0 +/- 32.9%, and overall release rate of 209.7 +/- 65.0 pg/2 minutes. Blockade of calcium activity with 10 microM verapamil and 4 mM EGTA suppressed the frequency and amplitude of the spontaneous pulsatile i beta-endorphin release (n = 2). Administration of 2 nM human CRF for 20 minutes at the end of 2 perfusions induced 205 and 883% increases of i beta-END release over the preceding basal levels. Administration of 2 nM CRF for 50 minutes at the end of another perifusion led to a greater and prolonged increase (maximum 4620% relative to the immediately preceding basal level) in i beta-END release. Addition of 56 mM KCl during the last 20 minutes of this prolonged CRF stimulation further increased i beta-END release (to 7680% relative to the baseline preceding the CRF stimulation). Each of 4 quarters of adult anterior pituitaries (2 quarters each from 1 male and 1 female) also released i beta-END in a pulsatile fashion, with a pulse interval of 11.8 +/- 2.0 minutes, pulse amplitude of 7.4 +/- 0.8 ng with nadir to peak increment of 51.4 +/- 15.3%, and overall release rate of 21.7 +/- 2.9 ng/2 minutes. These studies demonstrate that i beta-END release from the isolated human anterior pituitary in vitro is characterized by high-frequency pulses, independent of hypothalamic stimulation. This spontaneous calcium-dependent pulsatile i beta-END release apparently reflects the activity of an intrapituitary pulse-generating mechanism.

Adult↗

PubMed1988

Effects of the dopamine antagonist veralipride on hot flushes and luteinizing hormone secretion in postmenopausal women.

The effects on hot flushes of the dopamine antagonist Veralipride versus placebo were investigated in a randomized double-blind study of postmenopausal healthy women (N = 20 in each group). Cutaneous temperature recording and plasma LH pulsatility were studied in eight patients from each group. Veralipride administration (100 mg/day for 30 days) induced a significant (P less than .01) reduction in vasomotor symptoms and was more effective (P less than .05) than placebo. Treatment was followed by the expected increase (P less than .001) in plasma prolactin levels and by a significant decrease (P less than .05) in mean plasma LH. A significant reduction (P less than .01) was observed in objectively recorded hot flushes after Veralipride treatment, whereas there was no significant change in the characteristics of LH pulsatility. Infusion of the opioid antagonist naloxone (N = 5) induced a significant (P less than .01) increase in LH secretion after Veralipride administration. These results suggest that the endogenous opioid system may mediate the endocrine and clinical effects of long-term Veralipride treatment.

Climacteric↗

PubMed1988

Prevention of puerperal lactation by a single oral administration of the new prolactin-inhibiting drug, cabergoline.

To evaluate the efficacy of a single oral administration of the new ergot derivative Cabergoline in the prevention of post-partum lactation, we compared the effects of three different doses of the drug with those of placebo in 32 puerperal women. In a controlled, double-blind trial, the subjects were randomly allocated to four treatment groups receiving either placebo or 400, 600, or 800 micrograms Cabergoline (N = 8 in each group) within 24 hours after delivery. Treatment efficacy was assessed clinically by physical examination before (day 0) and at one, two, three, four, and 14 days after treatment. Plasma prolactin (PRL) concentrations were measured in blood samples collected before and at one, two, three, and four days after treatment. Lactation was prevented in four of the eight subjects (50%) who received 400 micrograms Cabergoline and in all subjects who received 600 or 800 micrograms Cabergoline. By contrast, only one of the eight subjects (12.5%) receiving placebo showed no signs of spontaneous lactation within the 14 days after delivery. No effects of placebo administration on plasma PRL levels were observed. Plasma PRL concentrations were significantly reduced starting from one day after Cabergoline administration, however, and the amount of inhibition of PRL secretion induced by different doses of the drug was not statistically different. These preliminary data demonstrate that Cabergoline has a dose-related effect in the prevention of postpartum lactation, and milk secretion can be prevented completely by a single oral administration of 600 or 800 micrograms of the drug.

Administration, Oral↗

PubMed1987

Intrinsic pulsatility of ACTH release from the human pituitary in vitro.

An in-vitro perifusion system was used to investigate spontaneous ACTH release from human fetal (21-23 weeks gestation) and adult pituitaries. The pattern of ACTH release from fetal pituitaries (n = 7) exhibited a remarkable pulsatile character with a mean (+/- SEM) pulse interval of 11.3 +/- 0.8 min. The mean pulse amplitude was 49.7 +/- 6.3 pg, with a nadir to peak increment of 90.7 +/- 10.4%. The mean ACTH release rate was 87.2 +/- 13.3 pg/2 min. Addition of the calcium chelator EGTA (4 nM) to the perifusion medium induced a significant (P less than 0.01) decrease in both ACTH release rate (from 102.0 +/- 8.5 to 52.0 +/- 9.9 pg/2 min) and ACTH pulse amplitude (from 57.7 +/- 2.8 to 31.3 +/- 4.6 pg) (n = 3). Administration of either 2 nM corticotrophin releasing factor (CRF) or 56 mM KCl induced 10- and 2-fold increases in ACTH secretion, respectively (n = 2). Quarters of adult human pituitaries (n = 6) also secreted ACTH in a pulsatile fashion, with a pulse interval of 14.8 +/- 1.7 min, pulse amplitude of 86.7 +/- 10.0 pg, nadir to peak increment of 84.5 +/- 9.8%, and overall release rate of 167.2 +/- 8.8 pg/2 min. These studies demonstrate that ACTH release from the isolated human pituitary in vitro is characterized by high frequency/low amplitude pulses, independent of hypothalamic stimulation. Accordingly, this spontaneous calcium-dependent pulsatile ACTH release apparently reflects the activity of an intrinsic intrapituitary pulse-generating mechanism.

Adrenocorticotropic Hormone↗

PubMed1987

Intrinsic pulsatility of luteinizing hormone release from the human pituitary in vitro.

An in vitro perifusion system was used to investigate the spontaneous luteinizing hormone (LH) release from 10 human fetal (21-23 weeks of gestation) and 1 adult female pituitaries. The pattern of LH release from fetal pituitaries (n = 6) exhibited a remarkable pulsatile character with a mean (+/- SE) pulse interval of 12.7 +/- 1.7 min. The mean pulse amplitude was 5.2 +/- 0.9 mIU with a nadir to peak increment of 69.5 +/- 6.4%. The mean LH release rate was 12.3 +/- 3.3 mIU/2 min. Blockade of calcium activity with 0.1 mM verapamil and 4 mM EGTA suppressed the frequency (from 1 pulse/12-20 min to 1 pulse/50-100 min) and amplitude (from 5.4-5.7 mIU to 1.4-2.1 mIU) of this spontaneous pulsatile LH release (n = 2). Administration of 8 nM gonadotropin-releasing hormone induced 255 and 954% increases in LH secretion (n = 2). Each quarter of an adult human pituitary also secreted LH in a pulsatile fashion, with a pulse interval of 15.2 +/- 5.6 min, a pulse amplitude of 5.4 +/- 0.6 mIU, a nadir to peak increment of 67.5 +/- 5.2%, and an overall release rate of 14.8 +/- 0.9 mIU/2 min. These studies demonstrate that LH release from the isolated human pituitary in vitro is characterized by high-frequency/low-amplitude pulses, independent of hypothalamic stimulation. Accordingly, this spontaneous calcium-mediated pulsatile LH release apparently reflects the activity of an intrinsic intrapituitary pulse-generating mechanism.

Female↗

PubMed1987

Dexamethasone reduces the postcastration gonadotropin rise in women.

To investigate the influence of glucocorticoids on gonadotropin release in humans, we studied the effects of dexamethasone (DXM) administration on basal and GnRH-stimulated gonadotropin secretion in normal women after bilateral ovariectomy (OVR). From the 7th to the 14th day after OVR, 9 women received DXM (2.25 mg/day) and 13 women received placebo (control women). Plasma FSH and LH concentrations were measured before OVR and daily from the 7th to the 14th day after surgery. In addition, the FSH and LH responses to exogenous GnRH (10 micrograms, iv bolus dose) were determined in all DXM-treated women and in 5 control women on the 7th and 14th days after surgery. Plasma gonadotropin levels increased similarly in all women on the 7th day after OVR. DXM administration significantly limited (P less than 0.001) the progressive rise of basal LH and FSH levels from days 7 to 14. DXM treatment also blunted (P less than 0.005) the OVR-induced increase in the responsiveness of both LH and FSH to exogenous GnRH. These findings suggest that glucocorticoids inhibit the secretion of both gonadotropins at the pituitary level in ovariectomized women.

Adult↗

PubMed1987

Pulsatile luteinizing hormone release in postmenopausal women: effect of chronic bromocriptine administration.

Pulsatile LH release was studied in 28 healthy postmenopausal women by obtaining blood samples every 5 min for 4 h either basally or after 30 days of bromocriptine (BCT; 3.75 mg/day; n = 14) or placebo (n = 14) administration. Basally, mean plasma LH levels were 46.3 +/- 3.5 (+/- SE) and 53.4 +/- 4.6 mIU/mL in the BCT and placebo groups, respectively. Mean LH pulse frequencies were 4.2 +/- 0.3 and 4.0 +/- 0.4 pulses/4 h, mean pulse amplitudes were 19.2 +/- 1.9 and 20.1 +/- 1.5 mIU/mL, and mean interpulse intervals were 54.3 +/- 3.1 and 54.6 +/- 3.2 min in the two groups, respectively. BCT administration induced no significant changes in mean plasma LH levels, but it significantly (P less than 0.01) decreased LH pulse frequency (1.7 +/- 0.3 pulses/4 h) and amplitude (12.7 +/- 0.8 mIU/mL) and significantly (P less than 0.01) increased mean interpulse interval (126.1 +/- 17.5 min). Placebo administration did not induce any significant changes in pulsatile LH release. These results demonstrate that in postmenopausal women LH secretion is circhoral, and BCT administration can blunt LH pulsatility, suggesting dopaminergic regulation of the GnRH-LH pulse generator.

Bromocriptine↗

PubMed1987

Dose-related prolactin inhibitory effect of the new long-acting dopamine receptor agonist cabergoline in normal cycling, puerperal, and hyperprolactinemic women.

Two different single doses (400 and 600 micrograms) of the new long-acting dopamine agonist cabergoline (CBG) were given to 12 normal cycling women, 17 puerperal women, and 24 hyperprolactinemic women (12 with idiopathic hyperprolactinemia and 12 with pituitary adenoma). Plasma PRL was determined in blood samples collected before and at frequent intervals for 5 days after CBG administration. Both CBG doses induced marked inhibition of PRL secretion in all women. A decrease in plasma PRL levels was evident 1-2 h after CBG administration and persisted for up to 5 days. The 600-micrograms CBG dose had a more potent (P less than 0.05) PRL inhibitory effect than the 400-micrograms dose in normal, puerperal, and hyperprolactinemic women. Moreover, while 400 micrograms CBG prevented lactation in 3 of 7 puerperal women, 600 micrograms CBG prevented lactation in 5 of 5 puerperal women. A moderate blood pressure decrease occurred 3-6 h after CBG treatment, but no other side-effects occurred. These results demonstrate that CBG induces a dose-related inhibition of PRL secretion in normal women as well as in puerperal and hyperprolactinemic women. The potent long-lasting PRL inhibitory effect of CBG in conjunction with the absence of side-effects typical of dopaminergic compounds suggest that this drug is an advance in the medical treatment of hyperprolactinemia.

Administration, Oral↗

PubMed1986

Effects of different dopamine agonists and antagonists on post-menopausal hot flushes.

The dopaminergic system seems to be involved in both pulsatile luteinizing hormone (LH) secretion and hot flushes in post-menopausal women. With the aim of further clarifying its role, the effectiveness of dopaminergic and antidopaminergic drugs in the treatment of hot flushes was studied. Self-assessed scores for vasomotor symptoms were evaluated in 5 groups of 15 patients treated for 20 days with one of the following agents: placebo; the dopamine receptor agonist, bromocriptine; the indirect dopaminergic agent, Liposom; the antidopaminergic drug, veralipride or the peripheral antidopaminergic agent, domperidone. All of these treatment regimens were effective in alleviating hot flushes, but the pharmacological agents proved to be more effective than the placebo. A direct dopaminergic action is hypothesized in the case of bromocriptine and Liposom, while the antidopaminergic drugs might act through different indirect mechanisms such as the short-loop feedback exerted by hyperprolactinaemia on tuberoinfundibular dopamine (TIDA) neurons with a secondary dopamine-like activity, or stimulation of the opioid system.

Bromocriptine↗

PubMed1986

GnRH release from the mediobasal hypothalamus. In vitro regulation by oxytocin.

The effects of oxytocin (OT) on gonadotropin-releasing hormone (GnRH) release from the adult male rat mediobasal hypothalamus and median eminence were studied in an in vitro incubation system. OT induced a dose-related (10(-13) to 10(-9) M) inhibition of both basal and KCl-stimulated GnRH release from the mediobasal hypothalamus. OT, but not arginine vasopressin, also inhibited GnRH release from the isolated median eminence, and this inhibition was blocked by treatment with an OT receptor antagonist. Moreover, antagonist alone stimulated GnRH release from the isolated median eminence. These results demonstrate that OT can inhibit in vitro release of GnRH by an OT receptor mediated mechanism at the level of neurosecretory terminals in the median eminence and suggest that the hypothalamic OT neuronal system may play an inhibitory role in the modulation of GnRH secretion.

Animals↗

PubMed1986

GnRH release from the mediobasal hypothalamus: in vitro inhibition by corticotropin-releasing factor.

The effects of corticotropin-releasing factor (CRF) on GnRH release from the adult male rat mediobasal hypothalamus (MBH) and median eminence (ME) were studied in an in vitro incubation system. CRF induced a dose-related inhibition of GnRH release from both the MBH and the isolated ME, and this inhibition was blocked by treatment with CRF receptor antagonist. Moreover, GHRF, a hypothalamic peptide similar in size to CRF, did not alter the ME release of GnRH. These results demonstrate that CRF can inhibit in vitro release of GnRH by a CRF receptor-mediated mechanism at the level of the neurosecretory terminals in the ME. Thus, increased hypothalamic CRF secretion associated with stress and adrenalectomy may inhibit hypothalamic GnRH release and produce the suppression of pituitary luteinizing hormone secretion which occurs under these conditions.

Animals↗