Effect of L-carnitine on motility and acrosome reaction of human spermatozoa.

L-carnitine added to the suspension medium decreases the glucose-sustained progressive motility of human spermatozoa. Addition of 20 mM L-carnitine to the capacitation medium causes an inhibition of the occurrence of the acrosome reaction parallel to a viability enhancement and negligible changes of the cellular content of ATP. The cellular efflux of glutamate-oxaloacetate transaminase was also inhibited by L-carnitine. A possible role of L-carnitine on membrane stability and metabolism of spermatozoa is briefly discussed.

Angiotensin-converting enzyme content of human spermatozoa and its release during capacitation.

In this study, we demonstrated, by using known detergents, the presence of angiotensin-converting enzyme (ACE) within human spermatozoa. We determined that maximal angiotensin-converting activity is expressed by sperm incubated in capacitating conditions, whereas this activity is negligible in saline-incubated spermatozoa. We further demonstrated that not acrosomes but cytoplasmic residues contain ACE. Because follicular fluid provides the necessary conditions for a maximal angiotensin-converting activity and for capacitations' metabolic activation, we hypothesize that ACE may play its physiologic role within the female reproductive tract.

Role of gonadal steroids in the serotoninergic control of prolactin secretion in men.

The physiological regulation of PRL secretion seems to involve the central serotonin system, since plasma PRL levels are enhanced by serotoninergic agonists and serotonin re-uptake blockers. The aim of this study was to evaluate whether the influence of oestrogens on PRL is mediated by the hypothalamic serotonin system. The PRL response to fenfluramine, a serotonin agonist that releases the amine and inhibits its re-uptake, was assessed in 10 normal men (aged 18-25 years) and in six castrated men (aged 18-24 years). In both groups, the effect of fenfluramine on PRL secretion was also evaluated on the sixth day after receiving clomiphene citrate, an oestrogen antagonist and partial agonist. In castrated men, fenfluramine administration was also performed on the seventh day after the last dose of testosterone enanthate (200 mg i.m. every 3 weeks for 4 months). Our results demonstrate that in normal men fenfluramine treatment significantly enhances plasma PRL levels, and clomiphene citrate treatment significantly reduces this effect. In castrated men, fenfluramine is also able to enhance PRL secretion but to a lesser extent; after clomiphene citrate treatment the increase of plasma PRL levels induced by fenfluramine rises to the normal range. We therefore suggest that in man oestrogens and aromatizable androgens influence PRL secretion at least in part by involving the activation of the hypothalamic serotonin system.

Evidence of sperm nuclear chromatin heterogeneity in ex-cryptorchid subjects.

Ex-cryptorchid subjects are frequently affected by infertility, even if the usually determined seminal parameters are still within the normal range. We evaluated in this study, in 14 ex-unilateral cryptorchid adult males (22-28 years), with normal sperm concentration, morphology and viability, the resistance of sperm nuclear chromatin to denaturation, using the fluorochrome acridine orange, which fluorescences green when bound to native DNA (double stranded) and red when bound to denaturated DNA (single stranded). Our findings demonstrate that the percentage of green-stained cells with acridine orange was significantly lower in our patients than in controls (p less than 0.001). We therefore suggest that the chromatin of ex-cryptorchid subjects' spermatozoa has a decreased resistance to denaturation and we hypothesize that this finding may explain the infertility of these patients, when the common seminal parameters are still within the normal range.

Calcitonin in human seminal plasma and its localization on human spermatozoa.

We determined the calcitonin (CT) levels in peripheral plasma and in seminal fluid of 15 normal human subjects: the concentration of the hormone in seminal fluid was about 30 times higher than the concentration found in peripheral plasma. We also studied the localization of calcitonin on human spermatozoa by means of an indirect immunofluorescent technique, using an anti-human CT rabbit serum and a fluorescein-isothiocyanate conjugated goat anti-rabbit immunoglobulins serum. A bright fluorescence was observed at the middle piece and neck, while the tail's principal piece was weakly stained. With an anti-human CT rabbit serum pre-absorbed with human CT no fluorescent staining was detectable. These findings demonstrate that calcitonin is localized onto spermatozoa and suggest a potential role for calcitonin in the calcium dependent-mechanisms of spermatozoa.

Possible significance of transferrin levels in seminal plasma of fertile and infertile men.

Human seminal plasma contains large amounts of transferrin, which is a protein secreted mostly by Sertoli cells. It has been suggested that the concentration of transferrin may serve as a possible clinical marker of Sertoli cell function. Therefore the concentration of this protein in human seminal plasma from fertile and infertile men has been evaluated in order to find a relationship between transferrin concentrations and human semen parameters and plasma FSH levels. Findings show that seminal transferrin in subjects with oligozoospermia or azoospermia is significantly lower than in controls, and that it is strongly related to sperm count. Results also indicate that transferrin secretion can be impaired when plasma FSH levels are still normal, suggesting that seminal transferrin is an early and specific marker of Sertoli cell function. These results, however, do not clarify whether impairment of transferrin secretion by Sertoli cells is due to an organic dysfunction or to an organic secretory alteration.

Localization of met-enkephalin on human spermatozoa and evidence for its physiological role.

Pro-opio-melano-cortino-derived peptides have been identified in rat testicular extracts and in human seminal plasma, but their physiological role is still unknown. We report that met-enkephalin is localized on human spermatozoa, by means of an indirect immunofluorescent technique. Furthermore, we demonstrate that a met-enkephalin analog (D-Ala2-Mephe4-Met-(o)-ol-enkephalin, FK 33-824, Sandoz, Basel, Switzerland: DAMME) inhibits in a dose-dependent manner the acrosome reaction induction. The hypothesis of a physiological role of seminal met-enkephalin on human spermatozoa fertilizing ability is briefly discussed.

Dopamine is not involved in the opioid control of luteinizing hormone secretion in man.

The aim of this study was to examine the role of the central dopaminergic system in the mechanisms by which opioid peptides exert their influence on luteinizing hormone (LH) secretion in man. The effects of sulpiride and naloxone on the changes in LH secretion induced by a metenkephalin analog (D-Ala2-MePhe4-Met-(o)-ol-Enkephalin, FK 33824, Sandoz, Basel, Switzerland) (DAMME) and dopamine infusion in four castrated men (21 to 25 years of age) were studied. In these patients, sulpiride pretreatment counteracted the inhibitory effect of dopamine but did not alter the fall of LH plasma levels that DAMME induced. Moreover, in these subjects naloxone reduced the inhibitory effects induced by DAMME but did not change the inhibitory effect of dopamine on LH secretion. These findings confirm that central dopaminergic and opiatergic systems play a role in the control of LH secretion; the data also exclude any interaction between these systems in regulating LH secretion.

Naloxone reduces the fenfluramine-induced prolactin release in man.

In order to ascertain whether there is a relation between opioids and the serotoninergic system in prolactin (PRL) secretion increase, we investigated in seven healthy men (21 to 26 years of age) the effect of naloxone, a specific opioid antagonist, on PRL secretion induced by fenfluramine, a drug that stimulates serotonin release and inhibits its re-uptake. We observed that subjects receiving fenfluramine (60 mg orally) had a significantly (P less than 0.001) higher increase in PRL plasma levels than the controls receiving placebo. In all subjects naloxone infusion at a dose of 15 mg caused a significant reduction (P less than 0.0005) in the PRL response to fenfluramine. Higher doses of naloxone (30 mg) do not further inhibit the PRL secretion induced by fenfluramine. These results suggest that naloxone may interact with opiate receptors on serotonin neurons thereby reducing the synthesis and release of serotonin. It seems that in man, therefore, there is an interplay between opiates and the serotoninergic system in the facilitatory influence on PRL release.