The effects of long-term (14-120 months) hCG-treatment of 17 male patients affected by isolated hypogonadotrophic hypogonadism (IHH) on testicular volume, plasma testosterone levels, and sperm concentration were assessed. Mean testicular volume increased from 3.8 +/- 0.2 (Mean +/- SEM) ml to a maximal of 14.9 +/- 1.1 ml after 22.2 +/- 2.3 months of hCG treatment. Maximal testicular volume correlated positively with the volume recorded before the patients had undergone any previous treatment. Testicular growth was also analysed by sorting the patients into two sub-groups according to whether their initial testicular volume was less than 4 ml (small testis subset, STS) or greater than or equal to 4 ml (large testis subset, LTS), supposedly indicating complete or partial gonadotrophin deficiency, respectively. Testicular volumes in the LTS group were always greater than those of the STS. Plasma testosterone levels reached adulthood values during hCG treatment and no statistically significant difference was detected between LTS and STS patients with IHH. Thirteen patients (70%) became sperm-positive during treatment with hCG alone; five out of eight (60%) were STS patients and eight out of nine (90%) were LTS. In addition, LTS patients always had a greater sperm output than did STS patients. Sperm concentration correlated positively with maximal testicular volume, but not with patient age, length of treatment, or initial testicular volume. The administration of hMG to eight of these patients caused an increase in testicular volume in two patients but the mean volume was not statistically different from that recorded at the end of treatment with hCG alone. Similarly, sperm concentration improved in three patients but again it did not differ significantly from that achieved in the course of hCG treatment. It is noteworthy that one patient became sperm-positive after the addition of hMG to his therapeutic regimen. Among sperm-positive patients attempting conception, seven out of 10 succeeded, two of whom were from the STS group. In summary, this study indicates that hCG alone is an effective treatment to induce complete spermiogenesis in IHH patients regardless of their initial testicular volume. However, a number of IHH patients may benefit from the addition of hMG in terms of testicular volume, sperm output, and pregnancy outcome.

The capacity to generate reactive oxygen species (ROS), both basally and after stimulation with the calcium ionophore A23187, was examined in the motile fraction of sperm isolated after swim-up from the semen of 10 naturally fertile men and three groups of infertile patients. The latter included: (1) men with a non-bacterial inflammation of the genital tract (n = 10); (2) men unable to impregnate their partners during an intra-uterine insemination programme (IUI) (n = 8) and their matched controls (n = 6); and (3) men with hypogonadotrophic hypogonadism (HH) who remained infertile after induction of spermatogenesis with gonadotrophin or gonadotrophin-releasing hormone therapy (n = 3) and their matched controls (n = 3). The levels of ROS production were elevated in the sperm of some infertile men with inflammation of the genital tract compared to those found in 10 naturally fertile men. In addition, sperm from those patients who remained infertile after an IUI programme produced higher amounts of ROS compared to their control group who became fertile. Similarly, the production of ROS by sperm from three patients with HH who remained infertile was significantly higher than those of the three men who became fertile. These data suggest that an excessive production of ROS by sperm may explain some cases of idiopathic male infertility.

The present study was undertaken to evaluate the serotonin (5-HT) receptor subtype(s) by which 5-HT acts on the pituitary to stimulate ACTH secretion. We tested the effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), the 5-HT1C receptor agonist metachloro-phenylpiperazine (m-CPP), which also binds to other 5-HT receptors with lower affinity, and the 5-HT2/1C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on basal, corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP)-stimulated ACTH release from primary rat anterior pituitary cell cultures. 5-HT, 8-OH-DPAT and DOI significantly increased basal ACTH release, an effect which was antagonized by 5-HT receptor antagonists. 5-HT and DOI were effective at nanomolar concentrations whereas 8-OH-DPAT was effective at higher concentrations. 5-HT, 8-OH-DPAT (both at 10 nmol/l) and DOI (at higher concentrations) blunted the stimulatory effect of CRH. The suppressive effects of 8-OH-DPAT and DOI on CRH-stimulated ACTH release were antagonized by (-)propranolol, a beta-adrenergic receptor antagonist which binds the 5-HT1A receptor with elevated affinity, and ketanserin, a 5-HT2 receptor antagonist respectively. 5-HT, 8-OH-DPAT and DOI showed additive stimulatory effects with AVP but only at the highest concentration tested, whereas m-CPP potentiated AVP-induced ACTH release at concentrations of 1 nmol/l or more. This effect was antagonized by metergoline, a non-selective 5-HT receptor antagonist and mianserin, an antagonist which binds the 5-HT1C receptor with elevated affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholecystokinin (CCK), a gastrointestinal (GI) hormone, is also present in structures of the central nervous system such as cortex, hippocampus, amygdala, olfactory tubercle and in regions involved in the regulation of the pituitary function. Although a number of studies have evaluated the effects of CCK on hypothalamic-pituitary-adrenal (HPA) axis function and on arginine vasopressin (AVP), prolactin (PRL) and growth hormone (GH) plasma levels in the laboratory animal, its role in humans has not been explored. Hence, we examined the effects of the exogenous administration of this GI hormone on corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol, AVP, PRL and GH plasma levels in humans. To accomplish this, graded doses (0, 50, 140 and 420 ng/kg) of sulfated CCK octapeptide (CCK-8), the full biologically active peptide, were infused intravenously to healthy men in 30 min. Blood samples were collected 30 min and immediately before the infusion was started (baseline) and 15, 30, 45, 60 and 90 min thereafter. CRH, ACTH, and AVP were extracted from plasma proteins using cartridges of SepPak C18. These hormones and cortisol were measured by radioimmunoassay whereas PRL and GH were measured by immunoradiometric assay. CCK-8 increased plasma ACTH and cortisol levels only at the dose of 420 ng/kg, whereas it had no detectable effect on plasma CRH levels. It increased also plasma AVP levels at the doses of 140 and 420 ng/kg. However, this effect reached the statistical significance only at the highest dose tested. CCK-8 stimulated PRL and GH release in a dose-dependent fashion. The lowest stimulatory dose was 140 ng/kg for both hormones. In conclusion, these results suggest that CCK is capable of stimulating HPA axis function, AVP, PRL and GH release in humans. Because these endocrine effects of CCK were detected at doses higher than that found able to mimic postprandial levels of this hormone, to produce Gl-related effects, and to modulate the release of GI hormones, we speculate that CCK, released by the GI tract, may not play a physiologic role in the regulation of the pituitary function in humans.

It has been hypothesized that there is an adrenal abnormality in the polycystic ovary syndrome (PCO). This study was undertaken to examine this hypothesis in a more physiological way, by enhancing the ACTH secretion in response to ovine corticotropin releasing hormone (oCRH) injection so that adrenal androgen and glucocorticoid responsiveness to endogenous stimulation could be examined. Plasma ACTH and the ACTH and cortisol (F) response to oCRH were normal. The plasma T and dehydroepiandrosterone (DHEA) responses were also normal. The androstenedione (A) response, however, was exaggerated. This study supports the hypothesis that the adrenal gland in patients with PCO produces increased amounts of androstenedione in response to ACTH stimulation.