Male infertility: is its rising incidence due to better methods of detection or an increasing frequency?
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Humans↗
Biomedical subjects
G Forti
Publications and source records attributed to G Forti.
Endothelin-1: a new autocrine/paracrine factor in rat testis.
Cultured Sertoli cells of 20-day-old rats were found to produce and release endothelin-1-like immunoreactivity (ET-1-LI) under follicle-stimulating hormone control. The elution profile of ET-1-LI from extracts of spent Sertoli cell culture medium corresponds to that of synthetic ET-1, suggesting a testicular production of authentic ET-1. In contrast, the conditioned medium from rat Leydig cells did not contain ET-1-LI. Immunohistochemical studies confirmed that, in 20-day-old rats, the positive staining was confined to some Sertoli cells, whereas interstitial cells were negative. In the adult rat testis the positivity was not limited to the tubular compartment (Sertoli cells) but was also present in the interstitium. A high concentration (13 pmol/mg protein) of high-affinity (dissociation constant = 0.6 nM) 125I-labeled ET-1 binding sites was present in Leydig cells. These sites bind ET-1 and ET-2 with 1,000-fold higher affinity than ET-3, suggesting that they correspond to the subtype ETA of the ET receptors. Specific 125I-ET-1 binding sites are present also in Sertoli cells but are 50-fold less concentrated than in Leydig cells. Our results suggest an autocrine/paracrine role for ET-1 in rat testis.
Animals↗
Immunolocalization of inhibin alpha-subunit in the human testis. A light- and electron-microscopy study.
The localization of inhibin alpha-subunit in the human testis was studied at the light- and electron-microscope level with immunostaining techniques. Antibodies against specific fragments of porcine and human inhibin alpha-subunits were utilized. At light microscopy, inhibin alpha-subunit immunoreactivity was detected in Sertoli cells, spermatocytes and in some Leydig cells. At electron microscopy, gold labeling was found in the cisternae of the Golgi apparatus and in the endoplasmic reticulum of Sertoli and Leydig cells. Gold labeling for inhibin was also found in coated vesicles in the cytoplasm of Sertoli cells as well as in coated pits and coated vesicles in the cytoplasm of some spermatocytes. The results of the present study suggest that, in the human testis, inhibin is produced by Sertoli and Leydig cells and is taken up by spermatocytes, on which it might act in a paracrine manner.
Coated Pits, Cell-Membrane↗
Sertoli-germ cells interactions in the human testis.
In previous histoimmunochemical studies we reported that transferrin (TF) and insulin-like growth factor I (IGF-I) are present in the cytoplasm of the Sertoli cells of the adult human testis. Receptors for TF were found mainly in adluminal germ cells and type I receptors for IGF-I both in Sertoli and germ cells. Using electron microscopy, evidence of transfer of both TF and IGF-I from the Sertoli to the germ cells through a receptor-mediated endocytosis mechanism was also found. In this paper we report the results of the histoimmunochemical localization of alpha inhibin in the human fetal, prepubertal and adult testis. In 8- to 14-week-old fetal testes a positive immunostaining was found mainly in the interstitial cells, whereas no staining was found in the germ cords. In the prepubertal testis the immunostaining was present in the Sertoli cells but not in the interstitial cells. In the adult human testis the immunostaining was present not only in the Sertoli cells but also in the spermatocytes and in several Leydig cells. Using electron microscopy and immunogold labeling the presence of alpha inhibin immunoreactivity was found in the rough endoplasmic reticulum and in the Golgi cisternae of both Sertoli and Leydig cells. Moreover we found evidence of transfer of alpha inhibin from the Sertoli to the germ cells through receptor-mediated endocytosis.
Adult↗
Frequency of prolactin pulsatile release in normal men and in agonadal patients is neither coupled to LH release nor influenced by androgen modulation.
OBJECTIVE: We wished to examine and characterize the prolactin pulsatile secretory pattern in both normal and agonadal males in order to assess whether there was any concordance with LH secretion. DESIGN: Patients were sampled every 5 minutes for 12 hours. PATIENTS: We studied five normal and four agonadal men, the latter group before and on testosterone enanthate (TE) (200 mg i.m. every 15 days) treatment. MEASUREMENTS: Prolactin and luteinizing hormone plasma levels were determined using commercial RIA systems. Pulse detection was performed using the DETECT program and the degree of concordance between luteinizing hormone and prolactin was established computing the specific concordance index. RESULTS: We demonstrated the presence of a frequent PRL secretory pattern in normal men (22.8 +/- 1.8 peaks/12h; mean +/- SEM) and in agonadal patients, both in basal conditions and during testosterone treatment (20.5 +/- 2.8 and 18 +/- 1.6 peaks/12h, respectively). The testosterone treatment in agonadal men significantly reduced luteinizing hormone pulse frequency (baseline: 27.5 +/- 2, testosterone administration: 18 +/- 1.3 peaks/12h, P < 0.01) but did not affect pulsatile prolactin release. Using a 10 and 15 minute sampling protocol, we observed that prolactin pulse frequency significantly decreased (P < 0.01) and was similar to the frequencies estimated in previous reports. When luteinizing hormone and prolactin time series were studied to evaluate the possible presence of a specific concordance (SC) between the secretory events of the two hormones, no significant degree of concomitancy was observed neither using the specific concordance index or the cross-correlation analysis. CONCLUSIONS: This report demonstrates (a) the presence of frequent pulsatile release of prolactin in both controls and agonadal patients (baseline and on testosterone enanthate), (b) the use of an appropriate sampling interval (5 minutes) to unmask the prolactin pulsatile release, (c) that in men, luteinizing hormone secretory events are not temporally linked to prolactin secretion, and (d) that androgens, even if reducing luteinizing hormone pulse frequency in agonadal patients, do not significantly affect prolactin pulsatile secretion, suggesting that testosterone and its metabolites do not affect lactotroph activity.
Adult↗
Spermatic and peripheral venous plasma concentrations of immunoreactive inhibin in prepubertal boys with undescended testis and in pubertal boys with varicocele.
To obtain more information about testicular inhibin secretion in the prepubertal and pubertal human male, we measured the concentrations of immunoreactive inhibin with a heterologous radioimmunoassay in the spermatic and peripheral venous plasma of 5 prepubertal boys with unilateral undescended testis (Group I, P1), 3 prepubertal boys with inguinal hernia (Group II, P1), and 12 pubertal boys with left idiopathic varicocele. The latter subjects were divided, according to the degree of their pubertal development, in early pubertal (Group III, N = 5, P2) and mid-pubertal groups (Group IV, N = 7, P3-4). In Group I, the mean (+/- SD) spermatic venous concentrations of inhibin (289.4 +/- 120.4 ml eq/l) were significantly higher than the corresponding mean peripheral venous concentrations (162.6 +/- 47.2; p < 0.02) suggesting active testicular secretion of inhibin. In Group II, the spermatic-peripheral inhibin gradient was not significant. In pubertal boys with idiopathic varicocele, the mean concentrations of spermatic inhibin were 1076.6 +/- 532.0 and 1023.4 +/- 274.5 in Groups III and IV, respectively. These levels were about five times higher than the corresponding peripheral concentrations (204.8 +/- 41.9 and 238.9 +/- 38.9; p < 0.005 and p < 0.001, respectively). When the data of all the boys were considered together the spermatic venous concentrations of inhibin were significantly correlated with those of peripheral venous FSH (r = 0.4749, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Child↗
Endocrine status in 29 patients treated by curative radiation therapy for nasopharyngeal carcinoma.
The basal endocrine status of 29 patients treated with curative radiation therapy for nasopharyngeal carcinoma was assessed; they were disease-free for a minimum of 4 years from the end of treatment. None showed clinical evidence of endocrine disease, and most of them had a substantially normal hormonal blood pattern. A slightly elevated TSH value, suggesting subclinical primary hypothyroidism, was found only in two male patients, which could be ascribed to the radiotherapeutic treatment of the neck. Although we cannot exclude more subtle alterations of hypothalamic-pituitary function, the percentage incidence of endocrine impairment in our patients seems lower than previously reported by other authors.
Adult↗
Growth factors in the human prostate.
Recent studies have focused on the potential role of local polypeptide growth-regulating factors in the etiology of benign prostatic hyperplasia (BPH) and prostatic carcinoma. In our studies we confirmed the presence of specific receptors for epidermal growth factor (EGF) in prostatic tissues from patients affected by BPH. In addition, we demonstrated that specific receptors for insulin-like growth factor type I (IGF-I) are present in BPH tissues. In order to identify a possible interaction between androgens and these growth-regulating factors, we investigated the effect of testicular suppression-induced androgen withdrawal on both EGF and IGF-I receptor concentrations in prostatic tissue from patients affected by BPH treated with a long-acting luteinizing hormone-releasing hormone analog. Both EGF and IGF-I binding capacities were significantly increased after treatment. This finding suggests that in vivo IGF-I and EGF receptor levels may be under negative androgenic regulation, indicating a potential role for these growth-regulating factors in the mechanism of response to the castration-induced regression of androgen-dependent prostatic tissue. Moreover, preliminary studies indicate that in human BPH prostatic tissue multiple IGF-binding proteins (IGF-BP) are present. This finding suggests a possible role of IGF-BP in modulating IGFs biological activities at the prostate level.
Aged↗
LDH and LDH-X activity in sperm from normospermic and oligozoospermic men.
Total lactate dehydrogenase (LDH) activity was measured in washed sperm from 74 oligozoospermic patients and 148 normospermic men. In the same samples, an additional iso-enzyme specific for germ cells, LDH-X was also measured. Both enzymatic activities were significantly higher in sperm from oligozoospermic patients than in those from normospermic men (P less than 0.001). In oligozoospermic patients, sperm LDH and LDH-X activities were related inversely to sperm concentration (r = -0.61 and r = -0.53, respectively). In normospermic men, this inverse relationship was less evident (r = -0.28 and r = -0.25, respectively). After separation of sperm on a discontinuous gradient of Percoll, LDH and LDH-X activities were increased in the non-migrated-sperm fractions and reduced in the migrated-sperm fractions in both groups of subjects when compared to the initial semen specimens. In addition, migrated sperm from oligozoospermic and normospermic men did not differ in their LDH and LDH-X activities. Although the possible contribution of immature germ-cells to these findings remains to be defined, the data suggest clearly that high levels of intracellular LDH and LDH-X are a biochemical feature of sperm from oligozoospermic subjects.
Centrifugation, Density Gradient↗
Epithelioid hemangioendothelioma of the liver: report of two cases.
Epithelioid hemangioendothelioma is a very rare tumour of vascular origin, the most peculiar feature of which is that it is composed of endothelial cells closely resembling epithelial cells. Confirmation of its endothelial origin is achieved by positive staining for Factor VIII-related antigen or by the demonstration of Weibel-Palade bodies by electron microscopy. We report two cases of primary epithelioid hemangioendothelioma of the liver that occurred in our center in the last ten years. The first patient is a 21 year old woman who presented with a right upper quadrant pain and an echographic finding of multiple hepatic lesions suggestive of metastases. The second patient is a 32 year old woman operated on for a cerebral glioma, in whom an abdominal CT scan, performed in view of radiotherapy, revealed multiple hepatic lesions, originally interpreted as being metastatic. In both cases, diagnosis was made based on the histologic examination of biopsies have been adopted in each case: the first patient has undergone successful liver transplantation. In the second patient an attentive surveillance appeared to be the best option, due to the presence of a previous cerebral glioma.
Adult↗
Pulsatile secretion of luteinizing hormone in agonadal men before and during testosterone replacement therapy.
UNLABELLED: We have reevaluated the question regarding the pulsatile pattern of LH secretion in agonadal men before and following testosterone replacement therapy. Five normal males were used as a reference group and four agonadal men were studied before and during replacement therapy with testosterone enanthate. All the subjects were sampled every 5 min for 12 h (08:00 to 20:00). Data were analyzed using the statistically based and validated pulse detection program DETECT. The normal subjects showed an LH pulse frequency of 10.2 +/- 1.7 peaks/12 h (mean +/- SEM) and a mean duration of 48.8 +/- 14 min, while in agonadal patients without testosterone replacement the frequency of LH peaks (27.5 +/- 2 peaks/12h) was significantly higher than for normal subjects (p less than 0.05), and the mean duration of peaks was lower than in controls (17.2 +/- 1.2 min; p less than 0.01). Following chronic testosterone enanthate replacement therapy (200 mg im every two weeks) these patients showed an increase in the duration and a significant reduction in the frequency of LH peaks (from 27.5 +/- 2 to 18.2 +/- 2.1 peaks/12 h; p less than 0.01) but pulse frequency remained significantly higher than for normal subjects (p less than 0.01). This finding is independent of the choice of p values for false positive detection rate (p = 0.01 or p = 0.005), but it does depend on sampling frequency and is influenced by large (four-fold) changes in the thresholds for peak detection. Using a "discrete deconvolution" technique we estimated the instantaneous secretory rate (ISR) for the two groups of patients. The results using ISR corroborated the findings obtained using analysis of observed plasma LH measurements. ISR computation also showed that the duration of the secretory events of the gonadotropes is significantly shorter (p less than 0.01) than the one estimated on plasma concentration, both in normal subjects and in agonadal patients before and during testosterone administration. IN CONCLUSION: LH pulse frequency observed in basal conditions in agonadal men was much higher than previously reported in primary testicular failure; during conventional testosterone replacement therapy LH pulse frequency of agonadal men was significantly reduced but still higher (p less than 0.01) than in normal men. This finding is probably related to the subnormal plasma levels of testosterone found in agonadal men during the replacement therapy; the analysis of data using a sampling interval of 10 min gave results similar to previous reports, confirming that the choice of sampling interval can markedly affect the evaluation of frequent LH pulsatile secretion.
Adult↗
Oral melanotic macules in patients infected with human immunodeficiency virus.
A group of 217 patients seropositive for human immunodeficiency virus (HIV) were studied for 2 years, during which time pigmented lesions of the oral mucosa developed in 14 (6.4%) of them. The lesions were well circumscribed in some cases and diffuse in others. In some patients the macules enlarged or recurred after surgical excision. In two patients the macules appeared during the administration of zidovudine. Clinical and laboratory evidence of adrenal insufficiency was not detected in any of the patients examined. The histologic appearances were those of melanotic macules. No ultrastructural alterations of the melanocytes were observed. Two of these macules also contained Epstein-Barr virus, and in one case normal oral mucosa was examined and also contained Epstein-Barr virus in the epithelial cells. As a control group we examined 180 health care workers who did not belong to any risk category, and 30 intravenous drug abusers who tested seronegative to HIV. Oral melanotic pigmentation was found in eight of the control subjects (3.6%). The difference was not statistically significant (p = 0.3097). Our study shows that oral macules do not occur more frequently in HIV-infected patients. However, the clinical behavior of these lesions appears to be different during the course of HIV infection. In some HIV-infected patients the cause of the macules might relate to the administration of zidovudine and antifungal or antibacterial drugs. In others the cause remains unknown and could be due to multiple factors.
Adult↗
Estimation of instantaneous secretory rate of luteinizing hormone in women during the menstrual cycle and in men.
In both men and women the pulsatile secretory pattern of LH has been extensively characterized. In the present study we used the algorithm for computation of instantaneous secretory rate (ISR) incorporated into the DETECT program to evaluate the secretory activity of gonadotrophs in vivo. We studied the pulsatile release of LH in four healthy women during four phases of the same menstrual cycle (early and late follicular and luteal phases) and in five healthy men. Computation of ISR permitted us to estimate the frequency and the duration of the secretory events from the gonadotrophs. Samples were collected every 10 min for 6 h. The apparent LH pulsatile frequency during the menstrual cycle varied from 5.0 +/- 0.8 (mean +/- SD) during the early follicular phase (EFP) to 5.3 +/- 1.2 peaks/6h during the late follicular phase (LFP), to 3.3 +/- 1.0 during early luteal phase (ELP) and to 5.3 +/- 0.4 peaks/6h during the late luteal phase (LLP). The mean pulse duration also changed throughout the phases of the cycle (EFP 47.4 +/- 13.2 min; LFP 55.4 +/- 21.6 min; ELP 100 +/- 50.4 min; LLP 48.1 +/- 11 min). In healthy men the LH pulse frequency was 3.8 +/- 1.6 peaks/6h and the duration was 71.5 +/- 35.7 min. When time series were analysed for ISR determination no significant changes were observed between the LH pulse frequency detected on ISR and that observed on plasma concentrations. Conversely, a significant reduction of the duration of the pulses was found when using ISR instead of plasma concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Gn-RH analogs and benign prostatic hypertrophy].
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Antineoplastic Agents↗
Extramedullary hematopoiesis involving the esophagus in myelofibrosis.
In this report, we describe a case of myelofibrosis with myeloid metaplasia; a 53-yr-old man was splenectomized for a massively enlarged spleen in which multiple foci of myeloid metaplasia were histologically demonstrated. The patient was referred to us for endoscopic examination, following the repeated occurrence of melena. Upper gastrointestinal endoscopy revealed two active ulcerative lesions in the bulb, and only a moderate erythema in the lower third of the esophagus, which showed no varices. There was no endoscopic evidence of active or recent bleeding. Subsequent histologic examination of biopsies taken from the esophageal lesion surprisingly revealed the presence of hematopoietic tissue.
Biopsy↗
Effects of surgery and general or epidural anesthesia on plasma levels of cortisol, growth hormone and prolactin in infants under one year of age.
Twenty infants under one yr of age undergoing minor surgery were divided in two groups according to the type of anesthesia (epidural, Group 1, n = 10; general, Group 2, n = 10) which was randomly performed. Blood samples for cortisol (F), growth hormone (GH), and prolactin (PRL) determination were taken from each infant in baseline conditions, before surgery, and at the end of surgery. Mean plasma F levels in infants of group 2 rose significantly (p less than 0.01) before surgery to attend a maximum at the end of surgery (p less than 0.005). In infants of Group 1 a significant increase was also observed before surgery (p less than 0.05) but at the end of surgery mean plasma cortisol returned to levels comparable to baseline. Mean GH plasma levels were not significantly affected by both types of anesthesia, however an increase (not statistically significant) was observed at the end of surgery in both groups. Mean plasma PRL levels showed a significant increase before surgery (p less than 0.05 and p less than 0.01 in group 1 and 2, respectively) and a further increase at the end of surgery in both groups of infants (p less than 0.005). These results suggest that in infants under one yr of age both types of anesthetic procedures preceding surgery have no significant effect on plasma GH, but produce a significant increase of cortisol and prolactin mean plasma levels. The cortisol response to surgery and general or epidural anesthesia was similar to that reported in adults and prepubertal boys.(ABSTRACT TRUNCATED AT 250 WORDS)
Anesthesia, Epidural↗
Sertoli cell proteins in the human seminiferous tubule.
It is well known that rat Sertoli cells in culture secrete both testis-specific proteins, such as inhibin and androgen binding protein (ABP), and proteins which are very similar, if not identical, to serum proteins, such as transferrin (TF), ceruloplasmin, and IGF-I. It is also well known that very few data have been reported about the secretory activity and the hormonal regulation of the Sertoli cell in man, mainly because of the difficulties associated with the isolation of pure cell populations from human tissue. Using histoimmunochemical techniques we tried to localize, with specific antisera, Sertoli cell proteins and, when possible, their receptors in the human testis. The results obtained with our Light Microscopy studies suggest that: (1) human Sertoli cells produce and/or store transferrin (TF), IGF-I, an albumin-like protein and ABP; (2) TF receptors are localized in spermatocytes and early spermatids and are absent in spermatogonia, in the cytoplasm of Sertoli cells and in differentiated spermatids; (3) IGF-I type I receptors are localized in the same germ cells and in the cytoplasm of Sertoli cells. The results obtained with our Electron Microscopy studies suggest that TF and IGF-I are internalized through a receptor mediated endocytosis mechanism both in Sertoli cells (basal compartment) and in germ cells (spermatocytes and early spermatids).
Androgen-Binding Protein↗
Three-month treatment with a long-acting gonadotropin-releasing hormone agonist of patients with benign prostatic hyperplasia: effects on tissue androgen concentration, 5 alpha-reductase activity and androgen receptor content.
The intraprostatic concentrations of testosterone (T) and dihydrotestosterone (DHT) have been measured in only a few men. We measured, in prostatic tissue obtained at surgery from seven men with benign prostatic hyperplasia, the effects of 3-month treatment with a long-acting GnRH agonist on 1) the intraprostatic concentrations of T, DHT, and 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol); 2) prostatic 5 alpha-reductase activity; and 3) the prostatic content of androgen receptors (AR). Plasma T, DHT, and 3 alpha-diol levels also were measured. Prostatic tissue samples obtained at surgery from a group of untreated men with benign prostatic hyperplasia also were studied. The mean DHT and 3 alpha-diol concentrations in the prostatic tissue of the treated men were about 10% of those in untreated men (n = 19; P less than 0.01 for DHT and P less than 0.05 for 3 alpha-diol), and the mean intraprostatic T concentration in the treated men was about 25% of that in the control group (0.10 greater than P greater than 0.05). The mean in vitro formation of DHT by the prostatic tissue of the treated men was about 50% lower (P less than 0.05) than that by prostatic tissue of the untreated men (n = 9). The mean cytosolic AR content in the prostatic tissue of the treated men was significantly higher (P less than 0.05), whereas the mean nuclear content of both salt-extractable and salt-resistant AR was significantly lower (P less than 0.05) than that in the prostatic tissue of the untreated men (n = 8). The mean plasma T levels in treated men decreased from 4.77 +/- 1.79 (SD) ng/mL (16.5 +/- 6.2 nmol/L) to 0.27 +/- 0.42 ng/mL (0.9 +/- 1.5 nmol/L) after 1 month of therapy and remained in the castrate range thereafter. We conclude that pharmacological castration resulting from 3-month treatment with a long-acting GnRH agonist decreases the intraprostatic T concentration to about one fourth and those of DHT and 3 alpha-diol to about one tenth of the levels in untreated men. Thus, GnRH agonist treatment may not completely abolish intraprostatic androgen concentrations in metastatic prostatic cancer patients. The decrease in prostatic 5 alpha-reductase activity as well as the decrease in nuclear receptors are probably secondary to the decrease in plasma T concentrations.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗