PubMed Health⌕ Search

Biomedical subjects

G Frajese

Publications and source records attributed to G Frajese.

At least 37 records · Page 2Linked to original sources
PubMed1991

Gonadotropin-induced expression of receptors for growth hormone releasing factor in cultured granulosa cells.

The hypothalamic neuropeptide, GRF, is formed in the ovary and acts via specific receptors in granulosa cells to enhance cAMP production and steroidogenic responses to the pituitary gonadotropin, FSH. Granulosa cells cultured without hormonal treatment displayed low levels of binding sites for GRF and the related neuropeptide, vasoactive intestinal peptide. However, treatment with increasing concentrations (50-500 ng/ml) of FSH caused dose-dependent increases in cAMP production and expression of binding sites measured with radioiodinated [His1, Nle27]human GRF(1-32)NH2, with no change in binding affinity. The maximum increase in GRF binding sites (2.2-fold) was elicited by 250 ng/ml FSH after 72 h incubation. GRF binding sites were also increased by agents that elevate intracellular cAMP, including choleragen, vasoactive intestinal peptide, dibutyryl cAMP, and forskolin. Low doses of forskolin that did not alone increase [125I] [His1, Nle27] human GRF(1-32)NH2 binding potentiated the action of FSH on GRF binding sites, but the effects of maximal stimulatory doses of both agents were not additive. These findings demonstrate that FSH promotes the expression of GRF receptors in maturing granulosa cells through cAMP-dependent mechanisms. Since GRF enhances the actions of FSH on cAMP production and granulosa cell differentiation, and GRF receptors are increased by the cAMP-mediated actions of FSH, locally produced GRF could exert a positive autoregulatory action to accelerate follicular maturation by amplifying the granulosa cell response to FSH.

Animals↗
PubMed1990

Neurotransmitter, opiodergic system, steroid-hormone interaction and involvement in the replacement therapy of sexual disorders.

Dopamine (DA) and serotonin (5-HT) are the neurotransmitters most directly involved in sexual activity. DA plays a stimulatory role while 5-HT has an inhibitory effect. The two monoaminergic systems modulate the secretion of many hormones (GnRH, LH, testosterone, prolactin and endorphins) involved in sexual functional capacity. Furthermore, hormones influence synthesis and storage of brain neurotransmitters. Impotence can often be associated to clinical depression and altered neurotransmitter function. Moreover, stress represents an unbalance between various neurotransmitter systems and can induce impotence especially when disorders of the endorphinic system are present. Replacement therapy is based upon the understanding of these basic concepts. Impotence due to an underlying depressive illness must be treated with dopaminergic antidepressant drugs; while in stressful conditions a good response to the naloxone test is the preliminary criterion to subsequent naltrexone treatment. When a hormonal deficiency has been proved, the hormone replacement therapy is of course highly effective (gonadotropins in hypogonadotropic syndromes, testosterone in aging, etc.). Finally, idiopathic impotence could be treated by DA agonist and/or 5-HT antagonist drugs either alone or better yet in association with psychotherapy.

Adult↗
PubMed1990

Plasma prolactin response to domperidone in acute schizophrenia and schizophreniform illness.

The prolactin (PRL) response to 20 mg of domperidone, a peripheral dopamine (DA) blocking agent, was evaluated in a group of 16 drug-free, acute, young schizophreniform and schizophrenic males and in a group of age-matched normal males. Although basal plasma PRL levels were normal, the PRL responses following domperidone were blunted in both patient groups. The PRL response was more blunted in the schizophreniform patients than in the schizophrenic patients. Possible explanations for these results include pharmacokinetic factors or abnormalities of the pituitary D2 DA receptors.

Acute Disease↗
PubMed1990

Prolactin and growth hormone responses to growth hormone-releasing hormone in acute schizophrenia.

Growth hormone (GH), and prolactin (PRL) responses to the administration of growth hormone-releasing hormone (GHRH) (1 microgram/kg) were evaluated in a group of 18 drug-free, acute, young male schizophrenics and in a group of age-matched normal controls. Cortisol responses were also evaluated. No difference in mean plasma GH, PRL and cortisol plasma basal values or in GH and PRL responses to GHRH between schizophrenics and controls was observed. Our failure to demonstrate a difference in GH response to GHRH between schizophrenics and controls would seem to indicate that GH secretory pituitary reserve is intact in young acute male schizophrenics. Cortisol values did discriminate between schizophrenics and controls (p less than 0.05). In our sample, both schizophrenics and normal controls showed a slight but significant (p less than 0.03) and transitory increase in plasma PRL response to GHRH.

Acute Disease↗
PubMed1990

Receptor-mediated actions of growth hormone releasing factor on granulosa cell differentiation.

GRF promotes follicular maturation and ovulation when administered with FSH in the treatment of infertility. Such actions could be mediated by stimulation of GH secretion and insulin-like growth factor I production, but the known actions of the structurally related hormone, vasoactive intestinal peptide (VIP), on granulosa cell function suggested that GRF may also act directly on the ovary to stimulate follicular development. Radioligand binding and activation studies, performed in granulosa cells from immature estrogen-treated rats, revealed a common receptor for VIP and rat (r) GRF in the ovary. Specific binding of [125I]VIP to granulosa cells was saturable and dependent on time and temperature. The relative potencies of VIP-related peptides for inhibition of radioligand binding were: VIP greater than rGRF greater than peptide histidine isoleucinamide greater than [His1,Nle27] human GRF(1-32)NH2 greater than secretin. In binding studies with the potent GRF agonist, [125I] [His1,Nle27]GRF(1-32)NH2, relative potencies were: rGRF(1-43)OH greater than [His1,Nle27]human GRF(1-32)NH2 greater than VIP greater than peptide histidine isoleucinamide greater than secretin. Glucagon and gastric inhibitory peptide, other peptides of the glucagon superfamily, and unrelated peptides including CRF and beta-endorphin, did not inhibit binding of either radioligand to ovarian receptors. In cultured granulosa cells, rGRF and VIP stimulated cAMP formation, consistent with coupling of their receptors to the adenylate cyclase system, and potentiated FSH-induced cAMP production. Both peptides also amplified FSH-induced progesterone biosynthesis, aromatase activity, and LH receptor formation. These observations demonstrate that rGRF is a potent cAMP-mediated agonist in the rat ovary and acts on a common VIP/GRF receptor in maturing granulosa cells. It is likely that the potentiating effect of administered GRF on gonadotropin-stimulated follicular development in vivo is in part mediated by direct actions of the peptide on the VIP/GRF receptor. Also, since GRF is present in the gonads, it is possible that the locally-produced peptide promotes follicular maturation by paracrine modulation of the stimulatory action of FSH on granulosa cell function.

Animals↗
PubMed1989

Reduced natural killer cell activity in major depression: neuroendocrine implications.

Natural killer cell activity (NKCA) was significantly reduced in a group of depressed patients, melancholic subtype, compared to sex- and age-matched controls. Corticotropin and cortisol values were significantly higher in the depressed subjects than in the controls, but no correlation between high hormone levels and low immunological activity was found in the patients.

Adrenocorticotropic Hormone↗
PubMed1989

Endorphins in male impotence: evidence for naltrexone stimulation of erectile activity in patient therapy.

In the present study we evaluated whether naltrexone administration could stimulate sexual function in 30 male patients, ages 25 to 50 years, with idiopathic impotence of at least one year's duration and not of organic etiology. The patients received naltrexone (50 mg/day) or placebo, on a random basis for two weeks. Sexual performance, expressed as the number of full coitus/week, was assessed before (time 0) and during (on days 7 and 15) each treatment. The naltrexone therapy significantly increased the number of successful coitus compared to placebo after 7 and 15 days of treatment: improvement of sexual performance was evident in 11 out of the 15 treated patients. All the patients experienced a significant increase in morning and spontaneous full penile erections/week. No significant side effects were reported. Endocrine studies revealed no significant modification of plasma LH, FSH or testosterone by naltrexone, suggesting that the positive effect of the drug on sexual behavior was exerted at a central level. A two-month follow-up, at which time patients were off treatment, erectile capacity had returned to baseline in 10 patients, while five reported complete recovery of their sexual ability. We hypothesize that an alteration in central opioid tone is present in idiopathic impotence and is involved in the impairment of sexual behavior.

Adult↗
PubMed1988

Corticotropin-releasing factor and adrenal function in major depression.

We investigated ACTH and cortisol responses after ovine CRF injection (1 microgram/kg one bolus) in a group of 11 drug-free patients suffering from major depression. When compared to sex- and age-matched normal controls, our depressed patients showed: Higher ACTH basal values (p less than 0.002); higher cortisol basal values (p less than 0.009); blunted ACTH response to oCRF administration (p less than 0.23); higher cortisol response to oCRF (p less than 0.001). Our data show that in depressed patients the feed-back mechanism is functionally intact at the pituitary level on one hand, while on the other, a hyperresponsiveness of adrenal cortex (even to minimal stimuli) seems to be present. Moreover, a hypersecretion of endogenous CRF in these patients seems to be likely.

Adrenal Glands↗
PubMed1988

Low serum bioactive luteinizing hormone in nonorganic male impotence: possible relationship with altered gonadotropin-releasing hormone pulsatility.

We determined the biological activity of serum LH in 23 men, aged 25-50 yr, complaining of nonorganic impotence of at least 1-yr duration and 20 normal men. All of the impotent men had normal general physical examinations, penile Doppler tests, psychological tests, and peripheral nerve conduction. Serum PRL, FSH, LH, and thyroid hormone concentrations were normal as were the results of provocative tests of TSH, gonadotropin, and PRL secretion. The mean serum immunoreactive LH (I-LH) levels, measured in each impotent and normal man in three samples taken at 15-min intervals, were similar [7.2 +/- 0.5 (+/-SE) vs. 6.4 +/- 0.5 mIU/mL (IU/L)]. In contrast, the mean serum bioactive LH (B-LH) level was significantly lower in the impotent men than in the normal men [15.9 +/- 2.1 (+/-SE) vs. 33.0 +/- 2.8 mIU/mL (IU/L); P less than 0.05], as was the LH bio- to immunoactive (B/I) ratio (2.1 +/- 0.2 vs. 5.6 +/- 0.5; P less than 0.02). The mean serum testosterone level in the impotent men, although all individual values were within the range of normal for our laboratory [200-900 ng/100 mL (693-3120 nmol/L)], was 25% lower than that in the normal men [347 +/- 23 vs. 450 +/- 26 ng/100 mL; P less than 0.05 (1204 +/- 81 vs. 1560 +/- 91 nmol/L)]. In addition, a significant positive correlation was found between serum testosterone levels and LH B/I ratios in the impotent men (r = 0.45; P = 0.029). Pulsatile LH secretion, measured in six impotent and four normal men in blood samples collected every 15 min for 6 h, was similar in the two groups. The mean serum I-LH levels were similar [7.5 +/- 1.1 (+/-SE) vs. 5.1 +/- 1.0 mIU/mL (IU/L)], while the mean serum B-LH level as well as the LH B/I ratio was significantly lower in the impotent men throughout the observation period [11.4 +/- 2.0 (+/-SE) vs. 26.0 +/- 3.2 mIU/mL (IU/L) and 1.4 +/- 0.2 vs. 5.4 +/- 0.6; P less than 0.05 and P less than 0.02, respectively]. The B-LH pulse amplitude in the impotent men was reduced [mean peak LH, 8.6 +/- 0.3 vs. 25.3 +/- 4.0 mIU/mL (IU/L); P less than 0.05], while the LH pulse frequency was similar in the two groups. The median intrapulse LH B/I ratios were significantly higher than the median interpulse ratios in both impotent (P = 0.02) and normal men (P = 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

Mechanism of action of ECT in major depressive disorders: a neuroendocrine interpretation.

Electroconvulsive therapy (ECT) is often efficacious in severe depression, and it is occasionally used in the treatment of schizophrenia. The mechanism of action of ECT is still poorly understood. We evaluated thyroid-stimulating hormone (TSH) and prolactin responses to thyrotropin-releasing hormone (TRH) after a first ECT and at the end of a series of seven ECTs in eight unipolar depressed patients with blunted basal TSH/TRH response, eight unipolar depressed patients with normal TSH/TRH response, and eight schizophrenic patients. The hormone patterns obtained after the first ECT showed an increase in prolactin and a decrease in TSH in all groups of patients, suggesting a nonspecific response. At the end of the therapeutic course, TSH responses increased in both groups of depressed patients, and the elevation was more relevant in depressed patients with normal TSH/TRH. Our data suggest that the mechanism of action of ECT becomes more specific when it is performed chronically and differs according to the organic substrate underlying different mental disorders. Moreover, an aminergic activation in the two groups of depressed patients seems to take place.

Adult↗
PubMed1987

Identification of calcitonin receptors in human spermatozoa.

Calcitonin (CT) is a powerful hypocalcemic hormone which regulates calcium balance in cells. The presence of CT and CT receptors has been demonstrated in many extrathyroidal tissues, including the male genital tract. CT immunoreactivity has also been found in human seminal fluid, and an inhibitory effect of salmon CT on human sperm motility in vitro was recently reported. In this study the presence of specific binding sites for synthetic salmon CT in intact human spermatozoa was investigated using [125I]salmon CT. Binding experiments demonstrated a CT-sperm interaction involving a receptor-mediated mechanism. The binding was very rapid and minimally reversible, with the maximal site saturation occurring at approximately 2 nM labeled peptide. The dissociation of the CT-receptor complex was only slightly influenced by the addition of unlabeled hormone. Increasing concentrations of unlabeled salmon, eel, and human CT produced a dose-dependent inhibition of [125I]salmon CT binding. These data fulfill the major criteria for demonstration of specific receptors for salmon CT in human spermatozoa. Owing to the key role of calcium ions in regulating sperm motility and the onset of the acrosomal reaction, CT receptors could be important in male gamete physiology.

Binding, Competitive↗
PubMed1983

Effect of long term administration of ovine prolactin on hypothalamic-pituitary testicular axis in rat.

The effect of hyperprolactinaemia on testicular morphology and on hypothalamic-pituitary-testicular axis was studied in adult male Wistar rats. Animals received ovine prolactin (oPRL) 200 micrograms twice daily s.c.) for 24 and 36 days and were killed by exanguination. Blood was collected for hormonal determinations and sex accessory glands were removed for histological studies. Circulating testosterone (T) and luteinizing hormone (LH) levels showed a significant reduction after 36 days of treatment whereas plasma follicle-stimulating hormone (FSH) levels were unchanged in all animals. No macroscopic or light microscopic histological modifications were observed in the testes. The present results, while excluding a direct effect of hyperprolactinaemia on seminiferous tubules, suggest that LH suppression is the consequence of a central effect of the ovine PRL long-term administration. The increased DA turnover in the hypothalamus suggested as inhibitory on GnRH neurons could account for this effect. The reduction of T levels seems to be mediated by the LH suppression, even though a direct effect of oPRL on Leydig cell receptors could be hypothesized.

Animals↗
PubMed1983

Reproductive parameters in prolactinaemic men.

The sexual behavior, hypothalamic-pituitary-testicular axis and seminal fluid parameters in three different models of hyperprolactinaemia were studied: patients with prolactin secreting pituitary adenomas, normal volunteers before and during metoclopramide, and psychotic patients on chronic neuroleptic therapy. Hyperprolactinaemia is always accompanied by a reduced seminal volume but there is no clearcut evidence that it can induce spermatogenesis modifications. Impotence is constantly present in the hyperprolactinaemic syndromes. The mildly impaired androgen production by the Leydig cells during hyperprolactinaemia does not seem to explain the impotence. Hypotheses on the pathogenesis of this symptom are suggested.

Adenoma↗
PubMed1982

Phospholipid liposomes and prolactin secretion: effects on spontaneous and drug-induced hyperprolactinaemia.

Bovine brain phospholipid liposomes (BC-PL) reduce plasma prolactin (PRL) levels in humans after acute administration and counteract the metoclopramide- and sulpiride-induced hyperprolactinaemia. However, BC-PL, like nomifensine, a dopamine (DA) reuptake inhibitor and therefore an indirect dopaminergic compound, does not influence TRH-induced hyperprolactinaemia. Moreover, BC-PL and nomifensine reduce plasma PRL levels in hyperprolactinaemic PCO syndromes but not in PRL secreting pituitary adenomas. The results obtained indicate that BC-PL antagonizes the DA blockade-induced hyperprolactinaemia and that the main site of action of BC-PL seems to be at the hypothalamic level; however a concomitant pituitary effect cannot be ruled out.

Adult↗