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Biomedical subjects

P Marrama

Publications and source records attributed to P Marrama.

At least 19 recordsLinked to original sources

Changes in glucocorticoid receptor immunoreactivity after adrenalectomy and corticosterone treatment in the rat testis.

The distribution of glucocorticoid receptor (GR) in the rat testis was investigated by means of immunocytochemistry (IR) and computer-assisted image analysis. A monoclonal antibody against rat liver GR showed the presence of GR IR selectively in the nuclei of interstitial and tubular cells. The semiquantitative microdensitometry of GR IR revealed that 77% of the specific staining was localized in the tubular compartment of rat testis. After adrenalectomy, GR IR was greatly reduced both in interstitial and tubular cells, roughly at the same degree. Corticosterone treatment (50 mg/kg, for 5 d) of adrenalectomized animals yielded a recovery of nuclear immunopositivity without changing the cellular distribution of GR, as observed in control rats. Nevertheless, the high dose of corticosterone administered produced a significant (p < 0.01) decrease of GR IR with respect to control rats. These results provide evidence for a prevalent nuclear binding of GR in the tubular compartment in basal conditions. On the other hand, adrenalectomy or repeated corticosterone treatment seem to affect GR similarly in all positive cells without changing significantly the proportion of GR IR in the different testicular compartments. This uneven distribution of GR IR suggests that tubular cells can be a major target of corticosterone when affecting directly testicular functions in the rat.

Adrenalectomy

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

Feeding and drinking responses to neuropeptide Y injections in the paraventricular hypothalamic nucleus of aged rats.

Neuropeptide Y (NPY), a peptide of the pancreatic polypeptide family, exerts a potent stimulatory action on eating when injected into the paraventricular hypothalamic nucleus (PVN) in rats. Several NPY-containing systems are altered with advancing age, and aged rodents develop anorexia and a modified daily cycle pattern of feeding. These findings suggest that a relationship may exist between the aging-related anorexia and the reduced function of NPY-containing systems projecting to the PVN. In the present study eating and drinking behavior in satiated or fasted young (3 months) and aged (24 months) rats have been investigated over 22 h after NPY injection into the PVN. The levels of NPY immunoreactivity (IR) in PVN were also evaluated by means of semiquantitative immunocytochemistry. NPY injections into PVN increased food and water consumption in both young and aged satiated rats 30, 90 and 240 min after injection. However, the feeding and drinking responses elicited by 0.05, 0.10 and 1.0 nmol of NPY were significantly attenuated in the aged rats when compared to young rats. In aged rats, 24 h of food and water deprivation produced significant increase of food consumption measured at 30, 90 min and 22 h, which was equivalent to that induced by 1.0 nmol NPY injection. Administration of 1.0 nmol NPY in PVN did not further increase the 24 h deprivation effect on feeding in both groups of rats, but enhanced drinking in deprived young rats. This effect was not present in aged rats. In addition, aged rats showed a stronger response to 24 h deprivation than to 1.0 nmol NPY administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Isolated adrenocorticotropic hormone deficiency secondary to hypothalamic deficit of corticotropin releasing hormone.

A 42-year-old man and a 51-year-old woman with a positive history of weakness and gastrointestinal complaints were shown to have low basal plasma cortisol and ACTH levels, and low daily urinary excretion of free cortisol. An empty sella was found in patient no. 1, while patient no. 2 was hypothyroid. Both patients showed a normal plasma cortisol response to ACTH and an increment in plasma ACTH and lipotropin levels after ovine CRH (oCRH), lysine vasopressin (LVP) and oCRH-LVP stimulation tests. These studies clearly report an isolated idiopathic ACTH deficiency due to a deficit in CRH in two adult subjects.

Adrenal Glands

Testosterone and erectile function, nocturnal penile tumescence and rigidity, and erectile response to visual erotic stimuli in hypogonadal and eugonadal men.

Further evidence that nocturnal erections are androgen-dependent and erectile responses to visual erotic stimuli are androgen-independent is presented from six men with secondary hypogonadism and six eugonadal controls. Erections during sleep were substantially less in the hypogonadal men, in terms of both tumescence and rigidity. In response to visual erotic stimuli, the percentage increase in circumference over baseline and the increase in rigidity were similar for the two groups.

Adult

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

Effects of prolonged treatment with diltiazem on pituitary secretion of luteinizing hormone, follicle-stimulating hormone, thyrotropin and prolactin.

In previous studies it has been observed that acute administration or short-term treatment with calcium channel blockers can influence the secretion of some pituitary hormones. In this study, we have examined the effect of the long-term administration of diltiazem on luteinizing-hormone (LH), follicle-stimulating hormone (FSH), thyrotropin (TSH) and prolactin (PRL) levels under basal conditions and after gonadotropin-releasing hormone (GnRH)/thyrotropin-releasing-hormone (TRH) stimulation in 12 subjects affected by cardiovascular diseases who were treated with diltiazem (60 mg 3 times/day per os) for more than 6 months and in 12 healthy volunteers of the same age. The basal levels of the studied hormones were similar in the two groups. In both the treated patients and the control subjects, a statistically significant increase (p < 0.01) in LH, FSH, TSH and PRL levels was observed after GnRH/TRH administration. Comparing the respective areas under the LH, FSH, TSH and PRL response curves between the two groups did not present any statistically significant difference. These findings indicate that long-term therapy with diltiazem does not alter pituitary hormone secretion.

Adult

Hypothyroidism increases vasoactive intestinal polypeptide (VIP) immunoreactivity and gene expression in the rat hypothalamic paraventricular nucleus.

Vasoactive intestinal polypeptide (VIP) is produced by neurons in the rat hypothalamic paraventricular nucleus (PVN) and may have an important role as a prolactin-releasing factor. Recent work from our laboratories has shown that thyroid hormone regulates the content of VIP and VIP mRNA in the rat anterior pituitary, but its effect on VIP in the PVN is not known. To determine whether thyroid hormone alters VIP biosynthesis in the PVN, we studied the effect of hypothyroidism on the content of immunoreactive (IR)-VIP and VIP mRNA in PVN neurons using histochemical techniques. By immunocytochemistry, only scattered IR-VIP fibers were present in the PVN of control animals whereas IR-VIP perikarya and fibers were present in hypothyroid rats. By in situ hybridization histochemistry, no labeled neurons were recognized in the PVN in control animals whereas PVN neurons were labeled in hypothyroid rats. These findings raise the possibility that hypothyroidism exerts negative feedback regulation on VIP-producing neurons in the PVN and suggest that this may be important to modulate the stimulatory effects of VIP on anterior and/or posterior pituitary function.

Animals

Sexual dimorphism of the autonomic nervous system response to weight loss in obese patients.

The sex-related response of the sympathoadrenal system to very low calorie diet (VLCD) with sodium restriction has been studied in a group of 16 obese subjects (8 men; 8 women). Once in sodium balance obese men were different from women in respect to initial body weight, mean daily 4 h urinary excretion of epinephrine (E) and norepinephrine (NE) measured for 48 h. After 20 days of VLCD the weight loss was higher in men than women (P < 0.01), E excretion increased in men more than in women (P < 0.01), and was correlated with weight decrement (r = 0.78; P < 0.01). NE excretion decreased in a similar way in both sexes. The present findings demonstrate sexual dimorphism in catecholamine excretion during VLCD and provide further evidence of the relative autonomy of adrenomedullary secretion from sympathetic nervous system activity.

Adolescent

High urinary excretion of adrenaline in insulin dependent diabetic subjects.

In view of the hyperglycemic and ketogenic actions of catecholamines, studies on the adrenergic pattern in diabetic patients are relevant to the management of diabetes. We have studied urinary adrenaline and noradrenaline excretion in 4-hour collections in 16 type I diabetic male patients without signs of autonomic or peripheral neuropathy and 11 age-weight matched controls. In diabetic patients adrenaline levels were higher than control subjects (26.8 +/- 3.9 vs 10.7 +/- 3.0 nmol/4h; p < 0.003) but did not differ in respect of noradrenaline (62.6 +/- 6.8 vs 59.6 +/- 10.8 nmol/4h) and creatinine excretion. This finding demonstrates a hyperactivity of the adrenal medulla in diabetic patients without concomitant elevations of noradrenaline. This occurred in absence of hypoglycemia and seems to be a common feature of type I diabetics without complications. Since these levels of adrenaline are sufficient to stimulate both lypolysis and glycogenolysis a previous characterization of adrenomedullary activity may help to better define insulin demands in diabetic patients.

Adult

Influence of exercise on dehydroepiandrosterone sulphate and delta 4-androstenedione plasma levels in man.

To study the involvement of adrenal cortex in prolonged physical exercise, we measured plasma dehydroepiandrosterone sulphate (DHEAS), delta 4-androstenedione (delta 4-A) and cortisol (C) levels in 20 moderately trained men one hour before and 5-10 min after one-hour-swimming. Mean plasma DHEAS and delta 4-A pre-exercise levels increased significantly with respect to post-exercise levels. Cortisol levels moderately increased, but showed no significant modifications after the exercise. These results suggest that in this physical exercise there is an independent activation of the cortical zona reticularis as to that of the zona fasciculata.

Adrenal Glands

Evidence of altered dopaminergic modulation of prolactin and thyrotropin secretion in patients with polycystic ovary syndrome.

In order to evaluate the functional activity of the tubero-infundibular dopaminergic system in polycystic ovary syndrome (PCOS), we analysed the prolactin (PRL) and thyrotropin (TSH) responses to the dopamine antagonist sulpiride. We studied 8 euthyroid women affected by PCOS and 7 normal women. The mean baseline PRL values were normal in both groups. After sulpiride administration the incremental area under the PRL profile in PCOS was significantly lower than in normal subjects (p less than 0.01). The mean basal plasma TSH levels were significantly higher in the PCOS than in the control group (p less than 0.01). After sulpiride administration the incremental area under the TSH profile was significantly lower in PCOS patients than in normal women (p less than 0.01). The higher basal plasma levels of TSH, the blunted response of PRL and the lack of response of TSH to sulpiride in PCOS suggest a relative decrease of the dopaminergic activity in PCOS patients.

Adolescent

[Urological and sexual evaluation of treatment of benign prostatic disease using Pygeum africanum at high doses].

This clinical study has been designed to evaluate the efficacy of an extract of Pygeum Africanum (Tadenan) (Roussel-Pharma) in patients suffering from prostatic hypertrophy or chronic prostatitis. The drug has been administrated to 18 patients, for 60 days, as double of standard dosage (200 mg/die per os, instead of 100 mg/die). Because of the high frequency of association of sexual disorders with those two pathologies, we have extended the study also to sexual disorders selecting patients suffering from prostatic hypertrophy or chronic prostatitis and, simultaneously, from sexual disturbances. No side effects have been observed during the treatment. The urinary disturbances have been evaluated by anamnesis and prostatic transrectal echography; sexual disorders have been evaluated by anamnesis and nocturnal penile tumescence and rigidity (NPTR) monitoring. Furthermore, dosage of serum levels of the hormones LH, FSH, Prolactin, 17 beta-Estradiol and Testosterone has been performed before and after therapy. Pygeum Africanum extract administration improved all the urinary parameters we investigated; prostatic echography relieved reduction of peri-urethral edema. Also an improvement of sexual behaviour has been obtained; but we have not found significant differences between serum hormonal levels before and after therapy, as well as for NPTR.

Aged

Effects of androgen treatment in impotent men with normal and low levels of free testosterone.

The relation between sexual function and serum free testosterone (fT) levels, which represent the active fraction of circulating testosterone, was evaluated. Two groups of impotent male subjects with mild hypogonadism were treated with oral testosterone undecanoate (TU); these men presented with tT/luteinizing hormone (LH) ratio and tT levels at the lower limits of normal. The first group had serum fT below 6.6 ng/ml, considered the lower normal value, according to our laboratory method, whereas the second group had normal fT limits. Administration of TU improved sexual function only in impotent men with low fT levels, but not in subjects with normal fT levels, even though the tT levels and the tT/LH ratio of the two groups were not significantly different. The results of our study suggest the presence of a minimum serum fT threshold, lying near the lower normal range, which determines the male sexual function. Moreover, serum fT levels were a more sensitive index than tT for identifying impotent men who can be successfully treated with androgens.

Adult

Sexual behavior of men with isolated hypogonadotropic hypogonadism or prepubertal anterior panhypopituitarism.

Sexual behavior of men with secondary hypogonadism was studied. Seven of the thirteen subjects presented with hypogonadism secondary to isolated gonadotropin (Gn) deficit, whereas the other six had idiopathic prepubertal anterior panhypopituitarism. Testosterone (T) levels were low and did not differ between the two groups. All subjects were evaluated both during replacement therapy (Gn in the first group; Gn plus cortisone and thyroxine in the second group) and 2 months after withdrawal of Gn therapy. During and after withdrawal of Gn administration, men with isolated deficit of Gn retained sexual activity and nocturnal penile tumescence, although they were partially compromised compared with a control group; on the other hand, panhypopituitarics reported compromised sexual function during Gn treatment and no sexual function when Gn therapy was not given. We conclude that different lesions of the hypothalamus-pituitary axis were accompanied by varying degrees of sexual impairment in the two groups of men presenting both secondary hypogonadism and very low T levels.

Adult

The effects of testosterone administration and visual erotic stimuli on nocturnal penile tumescence in normal men.

Nocturnal penile tumescence (NPT), as circumference change and rigidity, and REM sleep were measured in eight normal eugonadal men in two controlled experiments. In the first, exposure to erotic film prior to sleep had no effect on frequency of REM or on NPT. In the second placebo controlled experiment 150 mg im testosterone enanthate administration was associated with enhanced rigidity of NPT but with no effect on frequency or circumference change of NPT and no effect on frequency of REM.

Adult

Daily changes of neuropeptide Y-like immunoreactivity in the suprachiasmatic nucleus of the rat.

Most of the biochemical, physiological and behavioural events in living organisms show diurnal fluctuations, normally synchronized with 24-h environmental rhythms, such as the light-dark cycle. The suprachiasmatic nucleus (SCN) of the hypothalamus is considered to be a pacemaker of the circadian rhythms in several mammals. The light-dark cycle is the primary synchronizing agent for many of the circadian rhythms which are regulated by the SCN. The photic information reaches the SCN also through a neuropeptide Y(NPY)-like immunoreactive pathway from the ventro-lateral geniculate nucleus. We found that in 12-h-dark and 12-h-light housed rats the NPY-like immunoreactive innervation of the ventro-lateral part of the SCN shows a 24 h rhythm with values rising gradually during the light phase and falling during the dark phase. Besides this rhythm, we found two peaks corresponding to the switching on and switching off of the light. The average level of NPY-like immunoreactivity, as assessed by means of semiquantitative immunocytochemistry and expressed in 'arbitrary units', is reduced in rats housed in total darkness for 2 weeks. These results confirm the physiological role of NPY in the timing of the circadian activity of the SCN.

Animals

The endocrine effects of visual erotic stimuli in normal men.

Endocrine responses to erotic stimulation in the laboratory were assessed in eight normal subjects. Each subject was tested on two occasions. On one occasion only neutral stimuli were involved. After 15 min baseline, 30 min of films were shown. For the erotic condition on the other occasion, two 10-min erotic films were interspersed with 10 min of neutral film. Fifteen-minute blood samples were taken from the start of each test and continued for 5 hr after the films. Plasma was assayed for testosterone, LH, prolactin, cortisol, ACTH and beta-endorphin. Urine was collected for 4 hr before and 4 hr after the films; this was assayed for adrenaline, noradrenaline and dopamine. Sexual arousal occurred in response to the erotic films in all subjects, as shown by erectile and subjective responses. There were no significant changes in hormone or catecholamine levels following either the erotic or the neutral stimuli, except for a rise in cortisol during the neutral but not the erotic film. These results indicate that in the laboratory, substantial sexual response can occur without accompanying endocrine or biochemical changes.

Adrenocorticotropic Hormone