Stress management and erectile dysfunction: a pilot comparative study.

Erectile dysfunction (ED) is a complex disorder with various biopsychosocial implications leading the individual into a state of chronic stress that further worsens ED symptoms. The aim of this study is to investigate the effects of a 8-week stress management programme on erectile dysfunction (ED). A convenience sample of 31 newly diagnosed men with ED, aged between 20 and 55 years, was recruited during a period of 5 months to receive either tadalafil (12 patients) or tadalafil and the 8-week stress management programme. Both groups showed statistical significant improvement of both perceived stress and erectile function scores. Men practising stress management showed a statistical significant reduction in perceived stress score compared with men receiving tadalafil alone. No other statistical significant differences were noted between the two groups, although the stress management group showed a lower daily exposure to cortisol compared with the control group after 8 weeks. Finally, perceived stress and cortisol showed some interesting correlations with sexual function measurements. These findings provide important insight into the role of stress management, as part of the recommended biopsychosocial approach, in ED. Future studies should focus on randomised, controlled trials with larger samples and longer follow-up time.

Hyperprolactinaemia due to hypothalamic-pituitary disease or drug-induced in patients with erectile dysfunction.

One hundred and sixty-five patients with erectile dysfunction were assessed at the Athens Medical Sex Institute: 60 men (36.4%) considered their condition as organic, 52 (31.5%) rated it as mostly psychogenic, 45 (27.2%) thought it could be of mixed aetiology and 8 (4.8%) could not comment at all as to the aetiology. Initial psychologic evaluation rated the condition in the majority of cases as psychogenic (130 patients, 84.8%). No psychologist considered the erectile dysfunction as purely (100%) organic. After the urological and endocrine evaluation, vascular disorder was considered in 30 patients (18.2%), endocrine dysfunction in 16 patients (9.7%) and psychogenic in 109 patients (66.1%). Sixteen of the above patients had definite hyperprolactinaemia, two had large-sized prolactinomas as revealed by magnetic resonance imaging (MRI) and pituitary function tests. Four had nonfunctioning pituitary tumours, which was also based on MRI and pituitary tests. Four had small prolactin (PRL) adenomas. Drug-induced hyperprolactinaemia was suspected in six patients who used medications affecting PRL secretion and had no evidence of tumour on radiological evaluation. In conclusion, hyperprolactinaemia in men with erectile dysfunction needs to be evaluated before considering any other treatment.

Purification of functional lactotrophs and somatotrophs from female rats using fluorescence-activated cell sorting.

As the secretory granules of anterior pituitary cells fuse with the cell surface, there would appear to be sufficient hormone present on the cell surface to be labelled by polyclonal hormone antibodies and thus analysed by flow cytometry. We have therefore applied fluorescence-activated cell sorting to these labelled pituitary cells. Percentage purity and depletion of other cell types was assessed by immunocytochemistry and the reverse haemolytic plaque assay (RHPA). Results demonstrate that fluorescence-activated cell sorting allows almost complete purification of functional lactotrophs and somatotrophs to 96.7 +/- 1.7 (S.E.M.)% and 98 +/- 1.0% respectively by immunocytochemistry, and to 95.8 +/- 1.1% and 97 +/- 0.8% respectively by RHPA. Depletion of other anterior pituitary cell types to less than 2% was demonstrated by both immunocytochemistry and RHPA. Fluorescence-activated cell sorting to this degree of purity was routinely possible with cell yields of 91 +/- 3.4%. To obtain such purity/depletion, it was necessary to use specific antisera of high titre, at concentrations which ensured maximal cell-surface labelling associated with maximal stimulation of hormonal secretion by the appropriate hypothalamic stimulatory factor. Separating cells on the basis of the intensity of prolactin cell-surface labelling demonstrated a low level of binding of the prolactin antibody to gonadotrophs (but not of sufficient fluorescence intensity to be sorted into the prolactin enriched population), raising the possibility of prolactin receptors on gonadotrophs. We were unable to demonstrate the presence of mammosomatotrophs in the normal female rat, since purified lactotrophs did not contain or secrete GH nor did purified somatotrophs contain or secrete prolactin.

Flow cytometric analysis of functional anterior pituitary cells from female rats.

Laser-light scatter signals generated from living cells provide useful information with regard to both cell size (forward-angle light scatter) and granularity (ninety-degree or perpendicular light scatter). By measuring angles of light scatter and fluorescence, a fluorescence-activated cell sorter is capable of analysing and sorting cells on the basis of their size, granularity and cell-surface fluorescence. Using an electronically programmable individual cell sorter we were able to analyse single, viable, dispersed anterior pituitary cells of the female rat on the basis of their laser light scatter characteristics. Two distinct populations of differing granularity were defined: 26 +/- 2.2% (mean +/- S.E.M.) were more granular and 74 +/- 3.5% less granular. Acutely dispersed anterior pituitary cells were labelled with antibodies against four of the anterior pituitary hormones, and cell size and granularity were compared amongst the different hormonal cell types. Somatotrophs were the most granular cell type, gonadotrophs were the largest and corticotrophs the smallest, whilst lactotrophs were of intermediate size. Labelling was demonstrated to be dependent upon the secretory state of the cell. Hypothalamic stimulating factors increased cell-surface labelling, whilst dopamine and somatostatin decreased labelling. These changes compare favourably with published data obtained by immunocytochemistry. Using dual-colour fluorescence cell surface labelling we were unable to define a population of cells secreting both prolactin and growth hormone (mammosomatotrophs).

Comparative studies on the release of vasopressin and 7B2 from isolated hypothalami.

A new protein, 7B2, has been found in the anterior, intermediate and posterior pituitary and the hypothalamus. It has been previously suggested that 7B2 is synthesized in the hypothalamus and is transported to the posterior lobe in a similar way to vasopressin (AVP). We examined the in vitro release of AVP and 7B2, using rat hypothalami in a perifused column system. Membrane depolarization with KCl (56 mM) caused a marked stimulation of AVP release (from 116% to 263% above basal values). Release of 7B2 was also stimulated by potassium from 106% to 212% above basal values. Potassium pulses in calcium-free medium failed to release AVP or 7B2. Osmotic and cholinergic stimulation increased AVP secretion by 205% and 282% above basal values, respectively, but had no significant effect on 7B2 secretion. Chromatographic profiles of perifusion media revealed one immunoreactive 7B2 peak eluting at a coefficient of 0.34 corresponding to that of rat hypothalamic 7B2. Similarly AVP coeluted with AVP standard. Thus AVP and 7B2 are differentially released by cholinergic and osmotic stimuli in vitro.

Digoxin-like substance(s) interfere(s) with serum estimations of the drug in cirrhotic patients.

We measured the levels of digoxin-like immunoreactivity in the serum of 40 volunteers (20 patients with liver cirrhosis and 20 healthy adults) before and after the administration of a 5-day standard regimen of digoxin. Serum digoxin levels (SDL) were evaluated with two different radioimmunoassay (RIA) kits--Amerlex Digoxin 125I RIA and Digoxin 125I RIA. Digoxin was detectable by each RIA kit in 10 and 15% of controls and 50 and 60% of cirrhotic patients before the administration of the drug, respectively. At the end of the treatment with digoxin, SDL were significantly higher in cirrhotics when compared with those of controls. This study provides evidence that digoxin-like substance(s) is (are) implicated in the detection of high SDL in patients with histologically confirmed liver cirrhosis.

7B2, a new protein secreted by human functionless pituitary tumours, in vitro.

A novel pituitary protein, 7B2, of approximately 180 amino acids has been suggested to colocalise with LH in the pituitary gonadotropes. Increased secretion of LH is known to occur in functionless pituitary tumours. We have therefore measured 7B2 immunoreactive equivalents in the 24-h medium of explant pituitary cultures prepared from 17 functionless, 20 somatotropic, 16 PRL secreting and 8 corticotropic adenomas. A synthetic fragment corresponding to amino acids 23-39 of 7B2 was used to raise antisera (rabbits), prepare radiolabel (chloramine T iodination) and also serve as the assay standard. 7B2-immunoreactive equivalents in the medium from the functionless tumours was 517 +/- 149 pmol/l, significantly higher than that of the somatotropic tumours (248 +/- 90 pmol/l, P less than 0.05), prolactinomas (108 +/- 37 pmol/l, P less than 0.001) and corticotropin producing adenomas (107 +/- 77 pmol/l, P less than 0.001) (one-way analysis of variance). Gel permeation chromatography of medium obtained from functionless tumours revealed two immunoreactive 7B2 peaks one eluting at a coefficient of 0.28 corresponding to that of normal human pituitary extract and another eluting at a coefficient of 0.59. Gel chromatography profiles of medium obtained from somatotropic tumours contained similar immunoreactive 7B2 peaks (elution coefficient 0.28 and 0.57). These findings demonstrate that 7B2-like material is secreted by pituitary adenomas in explant culture with the highest level from functionless tumour cultures.

Effects of two novel dopaminergic drugs, CV 205-502 and CQP 201-403, on prolactin and growth hormone secretion by human pituitary tumours in vitro.

Two novel dopaminergic drugs, designated CV 205-502 and CQP 201-403 have recently been developed by Sandoz Pharmaceuticals Ltd (Basle, Switzerland). The effects of these drugs on PRL and GH secretion by normal rat and tumorous human pituitary cells in vitro have been investigated. Low doses of both CV 205-502 and CQP 201-403 immediately and profoundly suppressed PRL secretion, which failed to recover up to 7 h after removal of the drugs. Similarly, CQP 201-403 significantly suppressed basal GH secretion by human pituitary somatotropic tumours in culture, and both drugs significantly reduced the stimulatory effect of GHRH. These effects are more potent and longer acting than the previously described in vitro effects of bromocriptine. It is concluded that CV 205-502 and CQP 201-403 hold potential for the treatment of patients with hyperprolactinaemia and, possibly, also in patients with acromegaly.

Neuropeptide Y directly inhibits growth hormone secretion by human pituitary somatotropic tumours.

Neuropeptide Y (NPY) is a 36 amino acid peptide, widely distributed throughout the brain and is found in hypothalamic neurones. This latter finding suggests that NPY may possess a hypophysiotropic function. A number of studies have demonstrated effects of NPY on LH and GH secretion by rat pituitary cells. We report here the results of experiments investigating the effects of NPY on GH secretion by tumorous human somatotropic pituitary cells in culture. NPY (0.25-25 nmol/l) inhibited GH secretion by 20-53%, the maximal effect depending upon the tumour studied. The potency of NPY was less than that of somatostatin (SRIH). The stimulatory effects of growth hormone releasing factor (GHRH) and theophylline were reduced by NPY, but NPY did not modify the inhibitory effect of SRIH on GH secretion. It is concluded that NPY may be involved in the control of GH secretion, at least by tumorous human pituitary somatotropes.