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  • Author: A. R. Genazzani x
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F. Facchinetti, R. Bracci, M. G. Vanni and A. R. Genazzani


Cryptorchid boys show evident alterations in the fine structure of the testes, although they respond in a normal manner to various tests of endocrine function. On the other hand, there is evidence that glucocorticoids suppress plasma testosterone levels, although the mechanism is unknown. Eight control subjects and 8 bilaterally cryptorchid boys, at Pl stage of sexual maturation, were therefore studied by determining the degree of testosterone suppression induced by glucocorticoids. The subjects were submitted to a short dexamethasone (DXM) suppression (1.5 + 0.5 mg at 20.00 and 24.00 h, respectively) and to a short iv ACTH stimulation (1 U/m2 body surface). Basal concentrations of cortisol, androstenedione and testosterone were similar in both groups. Cortisol and androstenedione responded to both DXM suppression and ACTH stimulation in an identical manner in the two groups. DXM lowered the basal levels of testosterone by 46.4 ± 5.8% (mean ± se) in the controls, but only by 6.9 ± 6.6% in the cryptorchid boys (P < 0.001). ACTH only induced a significant decrease in the controls (from 110.9 ± 18.5 to 61.4 ± 10.9 and 72.3 ± 11.8 pg/ml (P < 0.025), after respectively 20 and 30 min), while no significant differences were found in the cryptorchid subjects.

These data indicate that in bilateral cryptorchidism, plasma T is not affected by exogenous (DXM) or endogenous (cortisol) glucocorticoids.

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A. R. Genazzani, J. P. Felber and P. Fioretti


Plasma immunoreactive ACTH (I. R. ACTH), immunoreactive human chorionic somatomammotrophin (I. R. HCS) and 11-OH steroids levels were measured during normal and pathological pregnancies. Plasma I. R. ACTH levels were found to be above normal during pregnancy, with a slight decrease near term. This observation correlates well with the recent description of human chorionic corticotrophin (HCC), i. e. a factor of placental origin possessing a high biological adrenocorticotrophic activity and presenting partial immunological cross-reaction with human ACTH. The 11-OH steroids levels, as measured by a fluorimetric method, increased regularly during pregnancy but, unlike ACTH, reached their highest value near term, I. R. HCS increased progressively until term when a slight decrease was observed.

In pathological pregnancies, I. R. ACTH levels behaved like other placental hormones. On the contrary, 11-OH steroids levels remained generally unmodified. Treatment with high doses of prednisolone caused no inhibition of the plasma I. R. ACTH and of plasma 11-OH steroids levels. These data suggest placental autonomy of the secretion of HCC and low adrenal responsiveness to endogenous ACTH variations throughout pregnancy.

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E. Brambilla, F. Petraglia, F. Facchinetti and A. R. Genazzani

Abstract. Anomalous anterior pituitary hormone responses to acute administration of TRH and LRH have previously been observed in patients with primary affective disorders (PAD), with TRH eliciting GH, FSH and LH rises, and LRH eliciting GH and Prl rises. We examined whether the same unusual responses were present also for beta-endorphin (β-EP) and beta-lipotropin (β-LPH) in 15 PAD patients, in 9 patients with secondary affective disorders (SAD), and in 7 controls. TRH (500 ug iv) elicited rises of β-EP plasma levels in 5 PAD and 2 SAD patients, and of β-LPH in 4 PAD and 3 SAD patients. LRH (150 ug iv) elicited rises of plasma β-EP levels in 2 PAD and 2 SAD patients, and of β-LPH in 5 PAD and 2 SAD patients. No rises of β-EP and β-LPH plasma levels were observed in PAD patients after saline administration, nor in the controls after TRH, LRH or saline administration.

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A. R. Genazzani, F. Cocola, P. Neri and P. Fioretti


The results of a study of HCS plasma levels and behaviour in normal and pathological pregnancies may be summarized as follows: a) HCS plasma levels gradually increase during normal pregnancy, reaching the highest values at the 38–39th week after the last menstrual period; in the last few days of pregnancy and just before labour a slight decrease is observed; b) in threatened abortion the behaviour of HCS plasma levels in successive assays clearly divides the cases ending in spontaneous abortion (low or decreasing levels) from those favourably resolved; c) in molar pregnancies the very low HCS plasma levels support the diagnosis; d) in Rhesus-isoimmunization the HCS plasma levels are near normal in all the cases in which the foetus is only slightly affected. On the contrary, very high levels were found in cases of foeto-placental hydrops and the rapid increase in HCS plasma levels in these cases seems to correlate with the appearance of hydropic conditions; e) in diabetic pregnancies, the HCS plasma levels are normal or slightly below normal; decreasing HCS values in subsequent assays preceded the intra-uterine foetal death (IUFD) in one case; two cases of juvenile diabetes treated with less than the required doses of insulin showed very high HCS values; f) in preeclamptic pregnancies the HCS levels are lower than normal and show no further increase after the 32–33rd week; several cases followed up for some weeks support this observation, and cases ending in IUFD or premature labour showed very low HCS levels; g) similarly, low HCS levels which failed to increase in subsequent assays are found in all the cases of foeto-placental dystrophy and multiple placental infarct; h) the cases of IUFD in uncomplicated pregnancies examined during the first 24 hours after the IUFD demonstrate normal or raised HCS levels in three cases where IUFD occurred before the 27th week, and below normal values in 7 out of 9 cases where IUFD occurred afterwards; i) higher than normal levels are demonstrated in twin pregnancies and pregnancies with large babies; j) a significant correlation between the foetal weight and the HCS levels is demonstrated if the plasma samples are collected at least five days before delivery; k) in prolonged pregnancy the observation of low HCS levels clearly indicates the presence of foetal post-maturity or chronic foetal distress; in fact, in uncomplicated prolonged pregnancies the HCS plasma levels are similar to those found in normal pregnancy at term.

All these data indicate the value of plasma HCS radioimmunoassay in an evaluation of the placental function and sustain the importance of its application during the whole pregnancy, and in the presence of any pathological condition of gestation.

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Th. Lemarchand-Béraud, A. R. Genazzani, F. Bagnoli and M. Casoli


Total and free serum thyroxine, plasma thyrotrophin (TSH) levels and, in some cases, the binding capacity of thyroxine-binding globulin (TBG) were measured in normal and premature newborns.

In both groups, an acute release of TSH was observed in the first few hours of life, but this was prolonged over a period of 10 days in the premature newborns. The release of TSH induced, in both groups, an increase of total and free serum thyroxine (T4), reaching thyrotoxic levels. The TBG binding capacity, however, remains normal.

This thyroid hyperactivity at birth reveals an important reserve of TSH in the perinatal period and the great metabolic needs of the foetus on the first day of life.

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F. Facchinetti, A. Grasso, F. Petraglia, D. Parrini, A. Volpe and A. R. Genazzani

Abstract. The circadian rhythm of plasma proopiocortin-related peptides was studied in 15 heroin addicts and in 6 sex- and age-matched controls. ACTH, β-lipotrophin, (β-LPH), β-endorphin (β-EP) and cortisol were measured by RIA either directly (cortisol), or after plasma extraction (ACTH) and Sephadex G-75 gel chromatography (β-LPH and β-EP) every 4 h from 8 a.m. to 8 p.m. and again at 8 a. m. the next morning.

The means of the two 8 a.m. measurements of β-LPH (2.67 ± 0.34 fmol/ml, mean ± se), ACTH (2.74 ± 0.71) and cortisol (218 ± 31 pmol/ml) levels in heroin addicts were significantly lower than those in controls (6.28 ± 0.61, 10.1 ± 0.74 and 364 ± 27, respectively, P < 0.01) while β-EP concentrations in heroin addicts (5.1 ± 0.6) were similar to those of healthy volunteers (6.44 ± 0.56). In controls, all three peptides and cortisol show a circadian rhythm of secretion, the lowest values being in the evening and the highest ones in the morning. Heroin addicts partially lack this phenomenon showing constant levels of the three proopiocortin-related peptides throughout the day, with a slight but significant decrease of plasma cortisol.

In the 7 subjects who took heroin throughout the study, no systematic changes were observed in the three proopiocortin-related peptides, while it seems that this group of addicts shows a cortisol decrease in the evening to a lesser extent than subjects receiving methadone maintenance only.

These data show a decreased basal β-LPH, ACTH and cortisol secretion in heroin addicts, despite normal β-EP levels. This would indicate that anterior pituitary proopiocortin synthesis and/or secretion is affected in these subjects, and that there is also some impairment in the structures controlling the circadian rhythmicity of ACTH and related peptides.

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S. Bernasconi, F. Petraglia, L. Iughetti, C. Marcellini, A. Lamborghini, F. Facchinetti and A. R. Genazzani

Abstract. In order to evaluate the secretion of betaendorphin in obese children and adolescents, we measured plasma beta-endorphin, ACTH and cortisol levels before and following administration of CRH (1 μg/kg). Fourteen normal weight and 22 obese subjects (weight excess ranging from 30 to 98%) were studied. Plasma hormone levels were measured by radioimmunoassay directly in plasma (cortisol, ACTH) and after silicic acid extraction and Sephadex G-75 column chromatography (beta-endorphin). Basal beta-endorphin levels in obese children were significantly higher than in controls (14.7 ± 1.8 vs 6.0 ± 0.6 pmol/l; mean ± sem). No differences were found in basal ACTH and cortisol levels. CRH administration significantly increased beta-endorphin, ACTH and cortisol levels in normal subjects and ACTH and cortisol levels in obese subjects. Plasma beta-endorphin levels in obese children and adolescents did not show any significant increment. These data confirm the higher than normal beta-endorphin plasma levels in obese subjects in childhood and demonstrate that CRH is unable to increase beta-endorphin levels, suggesting an impairment of the hypothalamo-pituitary control mechanisms or an extra-anterior pituitary source.

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A Gallinelli, R Gallo, AD Genazzani, ML Matteo, A Caruso, TK Woodruff and F Petraglia

Gallinelli A, Gallo R, Genazzani AD, Matteo ML. Caruso A, Woodruff TK. Petraglia F. Episodic secretion of activin A in pregnant women. Eur J Endocrinol 1996,135:340–4. ISSN 0804–4643

The aim of the present study was to determine the characteristics of activin A secretion in women with normal and abnormal pregnancy. With this purpose, a prospective study was done to evaluate the putative pulsatile pattern of serum activin A in serial specimens of blood collected during a certain amount of time (every 15 min for 3 h). A group of pregnant women (N = 24) participated in a crosssectional study. They were subdivided into three groups: healthy pregnant women (N = 8), patients with preterm labor (N = 8) and patients with gestational diabetes (N = 8) before and after insulin therapy. Secretory pulses of serum activin A were determined in all patients with a specific frequency and amplitude by using two different computerized analyses, i.e. DETECT and CLUSTER. Mean ± sem values of serum activin A were significantly higher in patients with preterm labor and gestational diabetes than in controls (p < 0.01), showing a significant decrease following insulin therapy in diabetic patients (p < 0.01). Specific pulses of serum activin A levels were observed in all women. The mean pulse frequency did not change significantly between healthy controls and the different pathological groups. Patients with gestational diabetes after insulin therapy showed a pulse frequency that was significantly higher than in controls (p < 0.05). When the mean peak amplitude of activin A pulses was evaluated, patients with preterm labor or gestational diabetes showed values that were significantly higher than in healthy pregnant women (p < 0.01). A significant, inverse correlation between pulse frequency and amplitude was found both in healthy pregnant women (p < 0.05) and in patients with gestational diabetes (p < 0.001). The present study showed that circulating activin A levels in pregnant women change in a pulsatile pattern whose pulse amplitude is modified in the presence of gestational diseases, such as preterm labor or gestational diabetes.

Felice Petraglia, Department of Obstetrics and Gynecology, University of Pisa, via Roma 67, 56100 Pisa, Italy

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F. Petraglia, C. Barletta, F. Facchinetti, F. Spinazzola, A. Monzani, D. Scavo and A. R. Genazzani

Abstract. Acute physical exercise stimulates the activity of the hypothalamus-pituitary-adrenal axis in man. In the present study we measured plasma adrenocorticotropin, beta-endorphin, beta-lipotropin and cortisol levels in 27 male trained athletes in basal conditions, 60 min before and immediately after an official competition. The endocrine responses were evaluated in different groups of athletes participating in races (100 m, 1500 m, 10 000 m) or in the disc throw. The athletes competing for the runs showed a statistically significant increase in plasma adrenocorticotropin, beta-endorphin, beta-lipotropin and cortisol levels after the race (P <0.01), whereas the disc throwers showed no significant change in the hypothalamus-pituitary-adrenal axis hormones after the competition. The percent increase in plasma adrenocorticotropin, beta-endorphin, beta-lipotropin and cortisol was higher in the athletes who run 1500 m and 10 000 m than in those participating in the short distance race (100 m). The present results showed that plasma proopiomelanocortin-related peptides and cortisol levels increase in trained athletes following running competition and that this increase is related to the duration of the physical exercise.

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To further evaluate the role exerted by endogenous opioids on LH secretion a naloxone challenge (0.08 mg/Kg b.w. i.v.) was performed in 23 healthy children at different stages of puberty, in 5 adolescents in different period of menstrual cycle, in 3 case of idiopathic precocious puberty (PP), in 7 cases of delayed puberty (DP), in 4 females affected by hypogonadotropic hypogonadism (HH) and in 6 patients affected by polycystic ovary disease (PCOD). Naloxone does not induce any significant change on LH plasma levels in prepubertal helathy children and in all the cases of PP and DP. Similarly there was no LH response in healthy adolescents neither in HH nor in PCOD, the response to naloxone appears only in preovulary and luteal phases. These data indicate that the central opioid system regulating LH secretion in humans is active only at more advanced stages of puberty and it does not seem to play a role in the beginning of sexual maturation. Moreover gonadal steroids seem to play a fundamental modulatory role on opioid-controlled LH secretion.