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Biomedical subjects

V Montanini

Publications and source records attributed to V Montanini.

At least 19 recordsLinked to original sources

Circadian rhythm of plasma testosterone in men with idiopathic hypogonadotrophic hypogonadism before and during pulsatile administration of gonadotrophin-releasing hormone.

OBJECTIVE: The aim was to investigate whether a pulsatile discharge of LH from the pituitary is necessary to achieve the circadian secretion of testosterone. DESIGN: The daily rhythm of the androgen has been studied in patients with idiopathic hypogonadotrophic hypogonadism (IHH) both in the absence of therapy and during pulsatile administration of gonadotrophin releasing hormone (GnRH). PATIENTS: Six patients with IHH and ten normal subjects were analysed. Blood sampling was performed at 2-hourly intervals, for 24 hours. The IHH patients then received synthetic GnRH i.v. at the rate of one pulse every 2 hours (10 micrograms/pulse). On day 11 of treatment, blood samples were taken for the rhythm analysis every 2 hours, for 24 hours. MEASUREMENTS: Plasma testosterone and LH were measured in the individual samples by radioimmunoassay. Evaluation of the rhythm was performed by cosinor analysis. RESULTS: A significant circadian rhythm of plasma testosterone was statistically validated in the normal subjects, whereas no rhythm was detected in the IHH patients in the absence of therapy. On day 11 of GnRH pulsatile administration the IHH patients showed normal testosterone levels and a statistically significant circadian rhythm of the androgen was evident, with acrophase between 0700 and 0800 h. Moreover, the amplitude, acrophase and mesor of testosterone rhythm in IHH patients in the course of treatment were statistically indistinguishable from the corresponding values in the normal subjects. Plasma LH did not show statistically significant circadian variations, either in the control group or in the IHH patients before or during therapy. CONCLUSIONS: We conclude that a physiological circadian rhythm of plasma testosterone can be obtained, in IHH men, by treatment with GnRH. Since the pulsatile administration of exogenous GnRH at constant doses induced a circadian rhythm in testosterone and no daily variations in LH were evident, we suggest that, although a pulsatile secretion of LH is probably necessary for the synchronization of the circadian rhythm with acrophase in the morning, the testosterone variations might be the results of a local testicular modulation of LH action.

Adult

Luteinizing hormone (LH) secretory burst duration is independent from LH, prolactin, or gonadal steroid plasma levels in amenorrheic women.

The possible presence of LH pulsatile secretion has been studied in patients with hypothalamic amenorrhea [LH plasma levels, less than 3 (n = 35) or greater than 3 IU/L (n = 18)], amenorrhea associated with hyperandrogenemia (n = 31), or hyperprolactinemia (n = 10). Patients were sampled every 10 min for 4 h, and LH plasma concentrations were determined by the use of an immunofluorimetric assay. The program Detect was used for both pulse detection and data deconvolution, i.e. for instantaneous secretory rate computation, on LH time series. The presence of episodic LH secretion was observed in all patients, and LH pulse frequency ranged between 3.5 +/- 0.3 and 3.8 +/- 0.2 peaks/4 h among the four groups. LH pulse amplitude was significantly reduced in patients affected by hypothalamic amenorrhea with LH plasma levels lower than 3 IU/L (0.7 +/- 0.1 IU/L; P less than 0.01) and significantly increased in patients with hyperandrogenic amenorrhea (6.8 +/- 0.3 IU/L; P less than 0.01) compared to levels in the other groups under study. Instantaneous secretory rate computation permitted the optimal resolution of the secretory events and demonstrated that the duration of gonadotrope secretory bursts ranged from 22.8 +/- 1.4 to 26.8 +/- 2.3 min in amenorrheic patients and did not depend on LH, PRL, or sex steroid plasma levels. In conclusion, the present study shows the presence of significant LH pulsatile release in amenorrheic patients, suggesting that in amenorrheic, as in normally cycling, women the secretory bursts from the gonadotropes have the same duration, despite the plasma LH, PRL, or steroid hormone levels.

Adolescent

Evidence of luteinizing hormone secretion in hypothalamic amenorrhea associated with weight loss.

The lack of plasma luteinizing hormone (LH) pulsatile pattern or episodic LH secretory bursts during night have been demonstrated in hypothalamic amenorrhea. The availability of both sensitive and specific immunofluorimetric assay and algorithm for pulse detection enabled us to reanalyze the question of whether or not patients with hypothalamic amenorrhea secrete LH in a pulsatile fashion. Seven women with secondary amenorrhea associated with weight loss and four normally cycling women were studied, sampling every 5 minutes for 8 hours. Control subjects were studied during four different phases of the menstrual cycle. In all amenorrheic patients, a frequent LH pulsatile secretion, with pulses of low amplitude, was found (10.7 +/- 1.4 peaks/8 h; mean +/- SEM). The pulse frequency was significantly higher (P less than 0.05) than any phases of the control group (early follicular: 7 +/- 0.4 peaks/8 h; late follicular: 6.8 +/- 0.6 peaks/8 h; early luteal: 4.3 +/- 0.4 peaks/8 h; late luteal: 7 +/- 0.3 peaks/8 h). The LH pulsatile release in amenorrheic patients showed a mean pulse duration and amplitude shorter than in any phase of the menstrual cycle of the controls. In conclusion, in weight-loss-related-amenorrhea, the major change was not the absence of the LH pulsatile release but its increased frequency with reduced pulse amplitude.

Adolescent

Circannual rhythm of plasma thyrotropin in middle-aged and old euthyroid subjects.

The circannual rhythm of plasma thyrotropin (TSH) was evaluated in 8,310 euthyroid, serially independent, young, middle-aged and old men and women. A statistically significant circannual rhythm of plasma TSH was validated, by the mean group-cosinor method, in the middle-aged and old men and women (p less than 0.05), with acrophase in December, whereas the young subjects did not show any rhythm. No significant correlation was found between TSH plasma levels and free thyroxine (fT4) or ambient temperature in any group. Moreover, plasma fT4 did not show seasonal variations.

Adolescent

Age-related changes in plasma dehydroepiandrosterone sulphate, cortisol, testosterone and free testosterone circadian rhythms in adult men.

The circadian rhythms of serum luteinizing hormone, follicle-stimulating hormone, testosterone (T), free testosterone (fT), sex hormone-binding globulin (SHBG), oestradiol, cortisol and dehydroepiandrosterone sulphate (DHA-s) have been investigated in 5 normal male adults and 6 elderly men. Circadian rhythms were detected statistically significant (p less than 0.05) by population mean cosinor analysis, for T, fT, cortisol and DHA-s in the young group. In the elderly population, serum cortisol showed a clear circadian rhythm, although with some phase modification, whereas DHA-s secretion lost its circadian rhythmicity. This demonstrates that ageing differently affects the two major adrenal functions, glucocorticoid and androgenic; further, the data suggest that an independent adrenal androgen-regulating system could be selectively impaired in the older subjects. In the elderly group the loss of T circadian rhythm was confirmed, but a statistically significant circadian rhythm of fT was recorded. It was characterized by a marked phase advance and not related with the SHBG modifications found in elderly men. This finding leads us to reconsider the role of fT, which appears more sensitive than total T, in studying circadian rhythm of gonadal androgen secretion.

Adult

Subnormal prolactin responsiveness to thyrotropin-releasing hormone (TRH) in women with primary empty sella syndrome.

Basal prolactin (PRL) levels and PRL responsiveness to thyrotropin-releasing hormone (TRH) were studied in 10 women with primary empty sella (PES) syndrome (mean age 38.2 yr). Hyperprolactinemia (34 to 72 ng/ml) was found in 5 patients (hyperprolactinemic PES, H-PES), whereas 5 patients showed normal (9.5 to 19 ng/ml) PRL levels (normoprolactinemic PES, N-PES). The results were compared with those obtained in 10 healthy women (mean age 32.8 yr, PRL = 7 to 15 ng/ml) and in 8 women with a PRL-secreting pituitary microadenoma (MA) (mean age 37.5 yr, PRL = 39 to 85 ng/ml). The mean basal levels of PRL were significantly higher in patients with H-PES (50.8 +/- 13.2 ng/ml) or MA (64.0 +/- 18.3 ng/ml) than in the control group (10.9 +/- 2.6 ng/ml, p less than 0.02) and in the patients with N-PES (13.9 +/- 3.7 ng/ml, p less than 0.02). In contrast, the relative maximum response (RMR) of PRL to TRH (peak PRL/basal PRL) was significantly lower in the patients with PES (both H-PES and N-PES) or MA (1.4 +/- 0.4, 2.3 +/- 0.7 and 1.2 +/- 0.2, respectively) than in the control subjects (3.6 +/- 1.1; p less than 0.02, less than 0.05 and less than 0.02, respectively). Our results show that the pituitary responsiveness to the acute stimulation with TRH is significantly decreased both in patients with a PRL-secreting pituitary MA and in those with PES. Therefore, the clinical value of the TRH test in distinguishing the PES syndromes from prolactinomas seems to be questionable.

Adenoma

Dynamics of plasma gonadotropin and sex steroid release in polycystic ovarian disease after pituitary-ovarian inhibition with an analog of gonadotropin-releasing hormone.

To assess the dynamics of the suppression and recovery of plasma gonadotropins and sex steroids during and after inhibition of pituitary-ovarian function by a long-acting agonist GnRH-analog (GnRH-A), eight patients with polycystic ovarian disease were treated with 12 micrograms/kg X day GnRH-A for 56 consecutive days. In response to GnRH-A, these patients had a sharp and pronounced decline of their initially elevated immunoreactive LH and bioactive LH (bioLH) levels. Plasma immunoreactive FSH levels declined more rapidly than did bioLH, but the FSH decline was less sustained. Plasma testosterone, androstenedione, and estrone (E1) levels also declined during GnRH-A administration. The pattern of plasma androgen decrease resembled that of bioLH. There was a positive correlation between bioLH and the two androgens (r = 0.85; P less than 0.05, by Spearman's rank correlation, for both hormones). Cessation of GnRH-A administration was followed by prompt progressive increases in gonadotropin and androgen concentrations to pretreatment values. FSH recovered faster than bioLH. BioLH plasma concentrations reached pretreatment values by day 28. The recovery of plasma androstenedione and testosterone levels correlated positively with that of bioLH. Although plasma E1 levels were higher during the recovery period than during treatment, they never reached the concentrations found during the basal period, whereas estradiol concentrations were slightly but not significantly higher than those in the basal period. As a consequence, the E1 to estradiol ratio, very high in the basal period, approximated unity during recovery. These data indicate that hyperandrogenism in polycystic ovarian disease is gonadotropin dependent and accompanied by a relative abundance of LH bioactivity basally and during GnRH-A administration. Thus, the relative increase in bioLH secretion appears to be independent of the rate of gonadotropin secretion and the circulating sex steroid concentrations.

Adolescent

Effects of luteinizing hormone-releasing hormone (LRH) upon bioactive and immunoreactive serum LH in patients with Turner's syndrome before and after oestrogen treatment.

One daily dose of 0.05 mg ethinyl oestradiol was administered to 5 patients with Turner's syndrome (mean age +/- SEM = 16.4 +/- 0.7 years) for 10 days. The effects of acute stimulation with luteinizing hormone-releasing hormone (LRH) (0.1 mg iv) on biologically active and immunoreactive LH were analysed before therapy and at the end of oestrogen treatment. Bioactive LH (BIO-LH) was measured by a sensitive and specific in vitro bioassay based upon testosterone production by mechanically dispersed mouse Leydig cell preparations. Immunoreactive LH (RIA-LH) was evaluated by a double antibody RIA method. Prior to oestrogen treatment, LRH induced a prompt rise in BIO-LH and RIA-LH levels, which reached peak values at 30 and 45 min, respectively. After oestrogen treatment, a delayed response (with peak values at 120 min) was observed for both BIO-LH and RIA-LH. Before oestrogen treatment, the mean bioactivity to immunoreactivity (B/I) ratio of LRH-stimulated LH showed a significant decrease from basal values (P less than 0.05). In contrast, after ethinyl oestradiol administration the mean LH B/I ratio increased significantly from basal values in response to LRH (P less than 0.05). The mean relative maximum response (delta %) for BIO-LH was significantly higher (P less than 0.05) in oestrogen-treated than in untreated patients, whereas the mean BIO-LH delta area was significantly lower in the former group (P less than 0.01). Similarly, oestrogens decreased significantly the mean RIA-LH delta area (P less than 0.05), whereas they did not affect significantly the mean RIA-LH delta %. The results further emphasize that oestrogens may change the quality of circulating LH.

Adolescent

Effects of acute stimulation with gonadotropin releasing hormone (GnRH) on biologically active serum luteinizing hormone (LH) in elderly men.

This study was designed to characterize the response pattern of biologically active LH (BIO-LH) after Gonadotropin Releasing Hormone (GnRH) acute administration in healthy elderly men, in comparison with normal young adult men. Serum levels of BIO-LH under basal conditions and in response to the iv injection of 0.1 mg synthetic GnRH were measured in 6 healthy elderly men (mean age 74.2 yr), as well as in 9 normal young men (mean age 27.4 yr). A sensitive in vitro bioassay, based upon testosterone production by mechanically dispersed mouse Leydig cells, was employed to assess LH biological activity. Levels of immunoreactive LH (RIA-LH) and basal testosterone (T) concentrations were determined by a double antibody radioimmunoassay technique. Mean basal levels of BIO-LH and RIA-LH were significantly increased in elderly men, compared to levels in young men, whereas the mean basal ratio of LH in vitro bioactivity to LH immunoreactivity (LH B/I ratio) and mean basal T concentrations were significantly lower in the elderly group. After GnRH administration, the B/I ratio of serum LH remained unchanged both in elderly and in young men. The mean relative maximum response for BIO-LH (BIO-LH delta %) was significantly lower in elderly men than in the younger male subjects, whereas mean BIO-LH response areas (BIO-LH delta areas) were not significantly different in the two groups. The mean peak response for both BIO-LH and RIA-LH was observed at 45 min in the elderly group and at 30 min in the younger subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Decrease in luteinizing hormone biological activity/immunoreactivity ratio in elderly men.

Basal serum concentrations of biologically active luteinizing hormone (BIO-LH), immunoreactive LH (RIA-LH) and testosterone (T), as well as the LH bioactivity/immunoreactivity (B/I) ratios were measured in 57 healthy, elderly male volunteers aged 60-94 yr. As a reference group, 53 healthy young men aged 18-49 yr were also studied. LH biological activity was assessed by an in vitro bioassay method based on testosterone production by mechanically dispersed mouse Leydig cell preparations in response to graded doses of LH. The mean BIO-LH and RIA-LH serum concentrations in the elderly men showed a significant increase (two- and three-fold, respectively, P less than 0.001, as compared with the values in the young men, whereas the mean LH B/I ratio and T values were significantly decreased (-22% and -43%, respectively, P less than 0.001). The decrease in the LH B/I ratio in elderly men led us to hypothesize that the ageing pituitary may secrete molecules of LH possessing a reduced bioactivity in relation to their immunoreactivity.

Adult

Further studies on the effects of heroin addiction on the hypothalamic-pituitary-gonadal function in man.

The effects of chronic heroin addiction on LH biological and immunological activity, as well as on total and free testosterone concentrations, were investigated in 8 active young male addicts. The results were compared with those obtained in 33 normal young men. In addition, the effects of naloxone (N) administration on LH bio- and immuno-potency were studied in 3 normal men. LH biological activity (bLH) was assessed by a specific and sensitive "in vitro" bioassay, based upon testosterone production by mechanically dispersed mouse Leydig cell preparations. Double antibody radioimmunoassay methods were employed to assess serum levels of immunoreactive LH (iLH), total testosterone (T) and morphine (M). Free testosterone (FT) concentrations were determined by RIA after an ultrafiltration procedure. Mean basal values of bLH, iLH, T and LH bio/immuno (b/i) ratio observed in heroin addicts were similar to those obtained in the control group. In contrast, serum levels of FT and the mean FT/T ratio were significantly reduced in heroin addicts. A significant decrease of LH b/i ratio was observed during N infusion in the normal subjects.

Adolescent

Effects of acute stimulation with luteinizing hormone-releasing hormone (LRH) on biologically active and immunoreactive serum luteinizing hormone (LH) in pubertal boys.

The responses of biologically active LH (BIO-LH) and immunoreactive LH (RIA-LH) to acute stimulation with LRH (0.1 mg iv) were studied in 8 pubertal boys (9-15 years, 2nd-4th Tanner's stage), and in 10 healthy adult men (20-46 years). Serum levels of BIO-LH were assessed by an in vitro bioassay method based upon testosterone production by mechanically dispersed mouse Leydig cell preparations. In pubertal boys the mean BIO-LH/RIA-LH (B/I) ratio of basally secreted LH was significantly lower than in adult men (1.2 +/- 0.2 (SEM) and 2.2 +/- 0.2 respectively, P less than 0.01). After acute administration of LRH the mean B/I ratio of circulating LH showed a significant increase from the basal value in pubertal boys (2.6 +/- 0.2, P less than 0.01 vs basal values), whereas no significant difference in LH B/I ratios were demonstrated throughout the study period in adult men (2.1 +/- 0.1, P = NS vs basal values). In agreement with this finding, the mean relative maximum response for BIO-LH (BIO-LH delta %) was higher in pubertal boys than in adult men (1702.7 +/- 500.3 and 499.6 +/- 65.4% respectively, P less than 0.05), whereas the mean RIA-LH delta % was similar in both groups (609.1 +/- 85.1 and 534.1 +/- 75.5% respectively, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Age and sex related variations in biologically active and immunoreactive serum luteinizing hormone.

Relatively recent data from the literature show some discrepancies between bioactive LH (Bio-LH) and radioimmunoreactive LH (Ria-LH) in different endocrinological conditions. In 202 subjects of both sexes we have studied biologically active and immunoreactive LH and their ratio (B/l ratio) pattern through life. The results show that in male puberty the in vitro bioassay method gives a more discriminating measurement of serum LH than the radioimmunoassay. The ratio between bioactive and immunoreactive LH is well correlated with the increase of serum testosterone levels from male prepuberty to adulthood. On the contrary, there is no difference of B/l ratio between prepubertal girls and fertile women, in spite of the different gonadotropin levels. Finally LH bioactivity increases less markedly in elderly men than in postmenopausal women. These data suggest that, among several factors which may influence not only the quantity but also the quality of LH secreted, gonadotropin secretion rate and sex steroid milieu play an important role and may partly explain the B/l ratio changes in the situations investigated.

Adolescent

Circadian rhythm of testosterone and prolactin in the ageing.

The role which testicular hormones have on the decrease of sexual function in ageing men is still uncertain, but of primary interest. Previously, it has been known that the impairment of Leydig cell activity is a causal factor in the decreasing sexual function in ageing men. The present study is an evaluation of some chronobiological aspects, which directly or indirectly concern the 'Gonadostat' in ageing men, in order to determine of any change of the hypothalamic-pituitary axis occurs during the ageing process. The results from a group of 18 young men aged between 21 and 37 were compared with the results from a group of 28 older men between the ages of 67 and 98. The daily variations of testosterone (T) levels were determined in both groups of men as its circadian rhythm is well known in adult men. Moreover, the nocturnal secretory pattern of prolactin (PRL) was studied in 6 of the 28 elderly men. When comparing the usual increase of T levels in adult men, which occurs in the morning, there were no significant differences found in the older group of men between early morning and evening. The PRL levels showed no nocturnal increase in 4 of the 6 men. A hormonal impairment in the central nervous system may, in fact, be associated with the testicular deficiency leading to the decrease in sexual function of ageing men.

Adult