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Biomedical subjects

C Carani

Publications and source records attributed to C Carani.

At least 37 records · Page 2Linked to original sources
PubMed1999

Role of oestrogen in male sexual behaviour: insights from the natural model of aromatase deficiency.

OBJECTIVE: In order to evaluate the role of oestrogens on human male sexual behaviour, the gender-identity, psychosexual orientation and sexual activity of a man with a congenital lack of oestradiol resulting from an inactivating mutation of the aromatase P450 gene was investigated. The psychosexual and sexual behavioural evaluations were performed before and during testosterone treatment and before oestradiol treatment, during three phases of different dosages of oestradiol treatment. DESIGN: The study was performed before (phase A) and during (phase B) testosterone enanthate treatment (250 mg i.m. every 10 days, for 6 months), during testosterone withdrawal (phase C), and during each of the following transdermal oestradiol treatments: 50 microg twice a week for 6 months (phase D); 25 microg twice a week for 9 months (phase E), and 12.5 microg twice a week for 9 months (phase F). MEASUREMENTS: Sexual behaviour was investigated by a sexological interview and by a 2-month self-reported daily diary performed during each phase of the protocol study. Furthermore, during each oestradiol treatment (phase C, D, E and F), a study of depression, anxiety trait and sexual behaviour was performed by the Beck Depression Inventory (BDI), the Spielberger Trait Anxiety Inventory (STAI) and the Golombok-Rust Inventory of Sexual Satisfaction (GRISS), respectively. Sexual orientation and gender-identity were evaluated by the BEM Sex Role Inventory (BSRI). Serum testosterone and oestradiol were measured during each phase of the study. RESULTS: Before oestradiol treatment (phase C), serum oestradiol was undetectable, while it rose to 356.1, 88.1 and 55.1 pmol/l during phases D, E and F, respectively. Before any oestradiol treatment, during phase D, phase E and phase F serum testosterone was 18.13, 0.72, 14.3 and 18.51 nmol/l, respectively. The patient's gender-identity as assessed by BSRI and by the sexological interview was clearly male. The psychosexual orientation evaluated by BSRI, by the sexological interview and by the analysis of the self-filled diary was heterosexual. Relevant modification of the patient's sexual behaviour occurred only during oestrogen treatment. This was more evident during both phase E and phase F, and concerned the behavioural parameters with an increase of libido, frequency of sexual intercourse, masturbation and erotic fantasies. A reduction of BDI and STAI scores was detected during the oestrogen phases. CONCLUSIONS: The study of the sexual behaviour in this man with aromatase deficiency suggests that oestrogens in humans do not affect gender-identity and sexual orientation but could have a role in male sexual activity.

Adult↗
PubMed1999

GH/IGF-I axis in azoospermia in primary and secondary hypogonadism: a study before and during replacement therapy.

The growth hormone/insulin-like growth factor-I (GH/IGF-I) axis was studied in 15 azoospermic patients and in 10 control men. Eight patients were affected by hypergonadotrophic hypogonadism and 7 by hypogonadotrophic hypogonadism. All were studied before and during replacement therapy with testosterone and gonadotrophin, respectively, using the alpha 2 adrenergic agonist, clonidine (clonidine test). The data demonstrate no differences in basal levels for IGF-I and for the GH response to clonidine in azoospermic patients, affected by primary and secondary hypogonadism, before and during replacement therapy when compared with control fertile men. In contrast to some studies which describe a reduced GH response in azoospermia and oligozoospermia, we conclude that basal serum levels of IGF-I and the GH response to clonidine are not impaired in azoospermic patients affected by primary hypogonadism before and after the restoration of normal androgenization, and in azoospermic patients affected by secondary hypogonadism, both before and after restoration of spermatogenesis.

Adolescent↗
PubMed1999

The effect of chronic treatment with GH on gonadal function in men with isolated GH deficiency.

Eleven adult males, previously submitted to neurosurgery because of a pituitary lesion (three with craniopharyngioma, three with clinically non-functioning adenoma and five with macroprolactinoma) were treated with recombinant GH for 12 months after the diagnosis of GH deficiency was made. Circulating FSH, LH, prolactin, testosterone, 17 beta-estradiol (E2), dehyroepiandrosterone (DHEA-S), androstenedione. 17-OH-progesterone (17OHP), IFG-I, and steroid hormone-binding protein (SHBG) levels were assayed before and after CG test at study entry and 6 and 12 months after GH treatment. A significant increase in plasma IGF-I levels was obtained after 6 and 12 months of GH treatment. In addition, CG-stimulated, but not baseline, testosterone levels showed a significant increase after 6 and 12 months of GH treatment when compared with study entry (9.6 +/- 0.5 and 9.9 +/- 0.5 vs 7.9 +/- 0.5 ng/ml; P < 0.05). Baseline, but not CG-stimulated, serum 17OHP levels were significantly increased only after 12 months of GH treatment (1.7 +/- 0.1 vs 1.4 +/- 0.1 ng/ml; P < 0.05). No significant difference was found as far as both basal and CG-stimulated E2, androstenedione, DHEA-S and SHBG were concerned. With regards to the semen analysis, only seminal plasma volume was significantly increased after 12 months of GH treatment (2.9 +/- 0.3 vs 1.7 +/- 0.3 ml; P < 0.05). No significant change in sperm count, motility and abnormal forms was observed. These data show that GH treatment displays a clear-cut effect upon Leydig cell function and increases the production of seminal plasma volume in fertile adult males with isolated GH deficiency.

17-alpha-Hydroxyprogesterone↗
PubMed1998

Mitochondrial membrane potential and DNA stainability in human sperm cells: a flow cytometry analysis with implications for male infertility.

Sperm cells from control donors of proven fertility and men from barren couples were studied by conventional procedures, i.e., light microscopy as well as flow cytometry. Light microscopy analysis of semen included the measurement of spermatozoa concentration, morphology, and motility. All the men from barren couples were asthenozoospermic at the conventional analysis of semen samples. Flow cytometry was applied to study two important parameters of sperm cells: mitochondrial membrane potential (MMP) assessed by the cationic dye JC-1 and DNA stainability with propidium iodide (PI). JC-1 staining was more reliable than the classical procedure used for this purpose, i.e., rhodamine 123 (Rh123) staining, and allowed us to show a positive correlation between MMP and spermatozoa motility. Regarding DNA analysis, a higher relative percentage of immature spermatozoa, showing a high accessibility of DNA to the intercalating PI fluorochrome, was found in men from barren couples compared to donors of proven fertility. The relative percentage of immature spermatozoa was significantly higher in semen from oligoasthenozoospermic subjects. Moreover, a positive correlation was found between immature spermatozoa, as evaluated by PI staining, and cells with depolarized mitochondria, as evaluated by JC-1 staining, suggesting that spermatozoa defective for nuclear maturity could be functionally defective cells. No correlation between immature spermatozoa determined by FCM and immature spermatozoa determined by light microscopy was found, suggesting that these two techniques assess sperm cell maturity at different levels.

Adult↗
PubMed1997

Screening for deletions of the Y chromosome involving the DAZ (Deleted in AZoospermia) gene in azoospermia and severe oligozoospermia.

OBJECTIVE: To evaluate the occurrence and prevalence of microdeletions of the Y chromosome involving the DAZ (Deleted in AZoospermia) gene in patients with azoospermia or severe oligozoospermia. DESIGN: Controlled clinical study. SETTING: University infertility clinic. PATIENT(S): Infertile men (n = 168) with nonobstructive, idiopathic azoospermia or severe oligozoospermia and normal LH. The control group consisted of proven fathers (n = 86). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen analysis; polymerase chain reaction amplification of the loci sY84, sY143, sY254, and sY255; serum FSH, LH, and T; testicular volume. RESULT(S): Deletions involving the sY254 and sY255 DAZ loci were found in three azoospermic patients and two men with sperm concentration < 1 x 10(6)/mL. Serum FSH was elevated in four patients and was normal in one. All five patients had decreased testicular volumes compared with controls. No deletions involving the sY84 and sY143 loci were found. The four loci were amplified normally in the control group. CONCLUSION(S): The estimated frequency of deletions involving the DAZ locus is 3% in azoospermic-severely oligozoospermic men consulting an infertility clinic. Polymerase chain reaction amplification of the DAZ locus is useful for the diagnosis of microdeletions of the Y chromosome. Deletions involving more proximal regions of the Y chromosome seem to be rare.

Adult↗
PubMed1997

cynDAZLA: a cynomolgus monkey homologue of the human autosomal DAZ gene.

A gene on the human Y chromosome, specifically deleted in azoospermic patients (DAZ: deleted in azoospermia), and a DAZ homologue (DAZH) on human chromosome 3, have been recently described. In the present work we report the isolation and characterization of the corresponding DAZH gene of the cynomolgus monkey (Macaca fascicularis), which we have named cynDAZLA (cynomolgus DAZ-like autosomal). Reverse transcription-polymerase chain reaction was used to amplify the monkey DAZ homologue, and sequence analysis revealed an open reading frame of 888 bp encoding 295 amino acids. Northern blot hybridization of different tissues to a probe derived from the cynDAZLA cDNA detected a transcript of 3.5 kb that, in the male, was expressed only in the testis. Comparison of the cynDAZLA sequence to autosomal DAZ homologues from human, mouse and Drosophila showed two RNA-recognition motifs (RRM) and the presence of only one DAZ consensus repeat compared with the seven repeats found in the human DAZ gene on the Y chromosome. The homology of the cynDAZLA cDNA compared with the human DAZH and mouse dazla cDNAs is 97.97 and 87.46% respectively. The identification of the monkey cynDAZLA enables further studies regarding the putative functions of DAZH, such as onset of expression and hormonal dependence of this gene.

Amino Acid Sequence↗
PubMed1996

The effects of clonidine on blood pressure, catecholamine and growth hormone release in hypogonadal men is preserved and not influenced by testosterone replacement therapy.

It has been demonstrated that castration impairs the hypotensive effect of clonidine in rat as well as its GH-releasing activity while testosterone replacement restores to normal the effects of alpha-2 adrenoceptor activation. Thus, these data point to main role of the gonadal steroid testosterone in modulating the effects of alpha-2 adrenergic activation on blood pressure, catecholamine and GH release in animal. Aim of the present study was to verify the activity of clonidine on blood pressure, catecholamine and GH release in human male hypogonadism before and after testosterone replacement. To this goal, 14 hypogonadal men (HP, age 33.8 +/- 2.9 yr; BMI < 25 kg/m2; 8 with hypergonadotropic and 6 with hypogonadotropic hypogonadism) received clonidine administration (CLON, 300 micrograms po at 0 min) before and after 3 months of testosterone replacement (testosterone propionate depot, 250 mg i.m. every 21 days). Ten normal adult volunteers (NS, age 31.5 +/- 1.9 yr; BMI < 25 kg/m2) were studied as control group. In all subjects, before and after clonidine administration, systolic and diastolic blood pressure (SBP and DBP), pulse rate (PR), norepinephrine (NE), epinephrine (E) and GH levels were recorded. In HP basal testosterone levels were lower than those in NS (1.25 +/- 0.3 vs 7.34 +/- 1.5 ng/ml, p < 0.05) and were restored to normal by hormonal replacement (6.91 +/- 1.3 ng/mL) in HP, both SBP and DBP as well as PR were normal in basal conditions and were not modified by testosterone replacement. Both before and during testosterone CLON lowered SBP, DBP and PR in HP to the same extent observed in NS. In HP, basal NE levels were lower than those in NS (0.85 +/- 0.15 vs 1.28 +/- 0.19 nmol/l, p < 0.05) and were restored to normal during testosterone replacement (1.25 +/- 0.13 nmol/l). On the other hand, basal E levels in HP were similar to those in NS (179 +/- 42 vs 197 +/- 38 pmol/l) and were not modified by testosterone therapy (167 +/- 28 pmol/l). In HP, both before and during testosterone replacement, CLON reduced NE (0.44 +/- 0.10 and 0.58 +/- 0.07 nmol/l) levels to the same levels recorded in NS (0.68 +/- 0.08 nmol/l). Basal GH and IGF-I levels in HP (1.15 +/- 0.5 and 234 +/- 42 micrograms/l, respectively) were similar to those in NS (1.18 +/- 0.4 and 221 +/- 38 micrograms/l, respectively) and were not modified by testosterone (1.35 +/- 0.6 and 256 +/- 32 micrograms/l, respectively). CLON administration induced a clear GH response in HP (F = 37; p < 0.001) which overlapped with that recorded in NS and was not modified by testosterone (F = 1.7; P = NS). Our present findings demonstrate that, differently from in animal, in man testosterone has no role in modulating the effects of alpha-2 adrenergic activation by clonidine on blood pressure, catecholamine and GH release. On the other hand, our data suggest the existence in male hypogonadism of a reduced basal noradrenergic activity which is restored by testosterone replacement.

Adult↗
PubMed1996

Prolactin and testosterone: their role in male sexual function.

The role of androgens in the sexuality of men is still not completely clear. Men with severe hyperprolactinaemia frequently show mild hypogonadism, and many complain of loss of libido and penile erectile dysfunction (ED). We studied the night-sleep related erections and the penile response to visual erotic stimuli (VES) in 44 men: 13 with severe hypogonadism (Group 1; serum testosterone < 1.4 ng/ml), 10 with mild hypogonadism (Group 2; serum testosterone 2-3.5 ng/ml), nine with severe hyperprolactinaemia and mild hypogonadism (Group 3) and 12 control men (Group 4). All of the patients complained of loss of libido and ED. Group 1 showed significantly impaired night erections when compared with any of the other three groups, but no differences were detected between Groups 2, 3 and 4. The penile response to VES did not show any significant difference between the four groups, but was lower in Group 1 than in Group 4. These data confirm that night erections are androgen-dependent, but also suggest that there are two thresholds for serum testosterone: one below which sexual behaviour is impaired with normal night erections, and a lower threshold below which night erections are also impaired. The penile response to VES was confirmed as being only partially androgen-independent. Furthermore, hyperprolactinaemia does not affect night erections or the penile response to VES, suggesting that its effect on libido and sexual behaviour is due mainly to modulation of the psychological pattern of the patient.

Adult↗
PubMed1995

Effect of testosterone replacement therapy on the somatotrope responsiveness to GHRH alone or combined with pyridostigmine and on sympathoadrenal activity in patients with hypogonadism.

There is evidence suggesting that androgens influence GH secretion in man. Our aim was to verify whether the GH releasable pool is preserved and influenced by testosterone replacement in male hypogonadism. To this goal, in eight male hypogonadal patients (HP, age 32.2 +/- 5.0 yr; Body Mass Index 23.9 +/- 1.1 kg/m2) before and after 3 months testosterone therapy, we studied the GH response to GHRH (1 microgram/kg iv) alone and combined with pyridostigmine (PD, 120 mg po), a cholinesterase inhibitor which likely inhibits hypothalamic somatostatin release allowing exploration of the maximal somatotrope secretory pool. Sixteen normal subjects (NS, age 30.1 +/- 3.5 yr; Body Mass Index 22.5 +/- 1.8 kg/m2) were studied as controls. The GH response to GHRH in HP was similar to that in NS (AUC, mean +/- SE: 1238 +/- 362 vs 1018 +/- 182 micrograms/L/h). PD potentiated to the same extent the GH response to GHRH in both groups (2092 +/- 807 and 2840 +/- 356 micrograms/L/h). After three month testosterone therapy, in HP the GH responses to GHRH alone (1352 +/- 612 micrograms/L/h) and combined with PD (1948 +/- 616 microgram/L/h) were unchanged. Also IGF-I levels in HP were similar to those in NS (222 +/- 42 vs 210.6 +/- 55.8 micrograms/L) and were unchanged during testosterone replacement (280 +/- 31 micrograms/L). As androgens have been reported to modulate sympathoadrenal activity in the rat, both before and during testosterone replacement, we also measured plasma catecholamine levels. Basal NE (p < 0.05) but not E levels were lower in HP than in NS; testosterone restored basal NE levels to normal without affecting basal E. delta absolute increase of NE and E (p < 0.05 and 0.01 vs baseline, respectively) after PD in HP were similar to those in NS and were unchanged during testosterone replacement. In conclusion, these results demonstrate that the GH releasable pool is preserved in male hypogonadism. As in this condition a reduction of spontaneous GH secretion has been reported, it could be due to neurosecretory dysfunction but not to pituitary impairment. Subtle alterations of sympathoadrenal activity seem to be present in male hypogonadism and reversed by testosterone replacement.

Adrenal Glands↗
PubMed1995

The effects of testosterone replacement on nocturnal penile tumescence and rigidity and erectile response to visual erotic stimuli in hypogonadal men.

Nocturnal penile tumescence (NPT) and erectile response to visual erotic stimuli (VES) were measured, by means of a Rigiscan device, in nine hypogonadal men, and repeated after 3 months of androgen replacement. The same assessments were carried out once in 12 eugonadal controls. The number of satisfactory NPT responses, in terms of both circumference increase and rigidity, were less in the hypogonadal men than the controls and were significantly increased by androgen replacement, confirming the results of earlier studies. In terms of circumference increase, erectile response to VES did not differ between the hypogonadal men and the controls, and did not increase with androgen replacement. In terms of rigidity, the erectile response to VES did not differ between hypogonadal men and controls. However, in terms of both duration and maximum level of rigidity, there was a significant increase following androgen replacement in the hypogonadal men. These new findings, in relation to rigidity, require a modification of the earlier formulation, which saw NPT as androgen dependent and erectile response to VES as androgen independent. NPT, and possibly spontaneous erections at other times, clearly involve an androgen sensitive system. Erectile response to VES predominantly involves an androgen independent system but may also be influenced by androgen sensitive mechanisms.

Adult↗
PubMed1995

Temporal changes in sulphated glycoprotein-2 (clusterin) and ornithine decarboxylase mRNA levels in the rat testis after ethane-dimethane sulphonate-induced degeneration of Leydig cells.

Short- (3-24 h) and long-term (4-50 days) changes in sulphated glycoprotein-2 (SGP-2) and ornithine decarboxylase (ODC) mRNA levels in the adult rat testis were studied following a single dose of ethane-dimethane sulphonate (EDS), to destroy the Leydig cells. Distribution patterns of SGP-2 and ODC labelling were consistent with prevailing expression of the two transcripts in Sertoli cells and germ cells, respectively. This pattern did not show appreciable changes following EDS administration. No labelling of SGP-2 mRNA was noted in the interstitium of control and EDS-treated rats. This finding indicates that Leydig cell death induced by EDS is not associated with increased SGP-2 mRNA levels, a phenomenon related to apoptotic cell death in many tissues. Semi-quantitative densitometric analysis of the preparations demonstrated differential changes in SGP-2 and ODC mRNA levels in the tubular compartment following EDS treatment. At 6, but not at 3 and 12, h following EDS administration, SGP-2 mRNA levels showed a significant increase, possibly secondary to a direct effect of the alkylating agent on Sertoli cells. A significant decrease in ODC mRNA levels was observed from day 7 to day 28, matching degenerative changes in the seminiferous epithelium. In contrast, a decrease in SGP-2 transcript levels was observed from days 21-35 after treatment. In conclusion, our findings demonstrate that SGP-2 mRNA, a putative marker of apoptosis, is not altered in the testicular interstitium during EDS-induced degeneration of Leydig cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Indole-pyruvic acid, a tryptophan ketoanalogue, antagonizes the endocrine but not the behavioral effects of repeated stress in a model of depression.

Increased glucocorticoid secretion is frequent in mood disorders and is normalized by long-term antidepressant therapy. Many antidepressants act by increasing central serotonin transmission. We investigated the effects of a serotonin precursor, indole-pyruvic acid (IPA), in an animal model of depression based on repeated exposure to unpredictable stress. Rats were divided in groups, and IPA (20 mg/kg), the tricyclic antidepressant imipramine (IMI) (5 mg/kg), or vehicle was administered daily during 3 weeks of repeated exposure to various stressors according to the procedure described by Katz et al [Katz RJ, Roth KA, Carroll BJ (1981): Neurosci Biobehav Rev 5:247-251]. After treatment, rats were evaluated for stress-induced exploratory behavior and killed 24 hr later. Serum corticosterone levels and glucocorticoid receptor (GR) immunoreactivity (IR) in the nuclei of neurons located in the hippocampal subregion CA1 were also measured. Rats exposed to repeated stress showed a lower exploratory behavior score (p < 0.01), higher basal corticosterone levels (p < 0.01), and stronger GR IR in the hippocampus (p < 0.05) than control rats. All of these effects were antagonized by IMI treatment. IPA administration did not affect the behavioral response induced by repeated stress (p < 0.01) but normalized serum corticosterone levels. In addition, IPA treatment produced a decrease in GR IR (p < 0.05 versus control group) that was not modified by exposure to repeated stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗
PubMed1993

Centrally administered neuropeptide Y fails to increase food intake but enhances hypoalgesia in spontaneously hypertensive rats.

The effects of intracerebroventricular (i.c.v.) administration of neuropeptide Y (NPY1-36) on food intake and pain sensitivity in hot plate test were studied in spontaneously hypertensive rats (SHRs) and in normotensive Wistar-Kyoto (WKy) rats. In satiated SHRs NPY1-36 failed to significantly increase intake at doses that produced a strong effect in satiated WKy rats (0.25-1.25 nmol). Conversely, both NPY1-36 and the C-terminal fragment NPY13-36, a putative selective agonist for the Y2-receptor for NPY, enhanced the spontaneously occurring hypoalgesia of SHRs, having no effect in WKy rats. The present results indicate that the NPY central systems involved in the control of regulatory functions are differently tuned in SHRs and WKy rats, suggesting possible involvement of these systems in the genesis of hypertension.

Animals↗
PubMed1993

Combined treatment with growth hormone and luteinizing hormone releasing hormone-analogue (LHRHa) of pubertal children with familial short stature.

We evaluated the 12 month growth of 18 pubertal children with familial short stature randomly assigned to clinical follow-up (group A), GH treatment alone (group B) and GH+LHRH analogue (LHRHa) treatment (group C). Height velocity increased significantly compared to baseline in groups A and B (4.7 +/- 0.4 vs 6.6 +/- 0.6 and 4.4 +/- 0.3 vs 8 +/- 1 respectively), but not in C (5 +/- 0.5 vs 6.5 +/- 0.4). Moreover in group B height and height prognosis standard deviation score SDS) also were higher (-2.2 +/- 0.2 vs -1.7 +/- 0.2 and 1.8 +/- 0.3 vs -1 +/- 0.2, respectively). Comparisons among the groups showed a significant increase in group B vs the other groups of height velocity SDS (3.9 +/- 1.3 vs 0.4 + 1 and 0.3 +/- 0.7) and of height prognosis SDS (-1 +/- 0.2 vs -2.4 +/- 0.3 and -2.4 +/- 0.3). In conclusion, after one-year treatment, GH seems to be more effective in stimulating growth than GH +/- LHRHa, even if studies of longer duration and/or follow-up are needed.

Adolescent↗
PubMed1993

[Melatonin secretion in Klinefelter's syndrome].

It has been observed that the pineal gland seems to modulate diencephalic neuroendocrine activity through its principal hormone, melatonin. In animals, melatonin inhibits the secretion and release of hypophyseal gonadotropins, probably by inhibiting hypothalamic releasing factors; in man, on the contrary, the administration of LHRH seems to have a stimulating effect on melatonin serum levels. In the light of this, in pathologies characterised by an imbalance in the hypothalamus-hypophyseal-gonad axis, it is possible to hypothesise variations in the secretion of melatonin and/or in its circadian fluctuations. In order to clarify further the relationship between the epiphysis and the hypothalamus-hypophyseal axis, the present study evaluated the pattern of melatonin secretion in a group of 16 patients with Klinefelter's syndrome. The circadian rhythm of melatonin secretion was determined from venous blood samples taken at 9 am, 1 pm, 5 pm, 9 pm, 1 am and 5 am; the same protocol was also followed in two control groups of respectively prepuberal and puberal healthy subjects. During the night samples were taken as rapidly as possible, using a red light source in order to not interfere with melatonin secretion. All of the examinations were performed during the winter period. Serum levels of melatonin were determined, after extractions with diethylether, by means of a double antibody RIA using commercially available kits (Bioscience Product--The Netherlands). Intra- and inter-assay coefficients of variation were respectively 3% and 8%. The data are reported as mean values +/- SD; the results were analysed by means of Student's test for unpaired data and analysis of variance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗