Effects of corticosterone on reproduction in male Sprague-Dawley rats.

Corticosterone, the predominant circulating adrenal corticosteroid in rodents, was investigated for its effects on reproduction in male Sprague-Dawley rats. Male rats (in groups of 50, 25, and 50) were administered corticosterone at doses of 0, 10, and 25 mg/kg/d, respectively, by subcutaneous injection once daily for 6 weeks; the highest dose was decreased to 20 mg/kg/d after 15 d. During the last 2 weeks of the 6-week treatment period, 25 males per group were paired with untreated females. The remaining 25 males from the 0 and 25/20 mg/kg/d groups were allowed a 6-week recovery period and, during the last 2 weeks of this period, these males were also paired with untreated females. At the end of the treatment period, the males had markedly elevated plasma corticosterone concentrations and decreased weight gain. They also produced fewer copulatory plugs than controls, which may have been secondary to observed adverse effects on the accessory sex organs (decreased weights and microscopic changes in prostate and seminal vesicles). However, no adverse effects on sperm motility, sperm count, or microscopic features of the testes were observed. Serum testosterone concentration of the high-dose males was elevated, but luteinizing hormone was unaffected. The numbers of embryonic implantation sites and live fetuses in females mated to these males were reduced. All of these effects except decreased prostate weights were reversible upon cessation of corticosterone administration. Thus, exogenous administration of corticosterone to male rats produced reversible effects on implant count and litter size of female rats mated to these males. These effects on male rat reproduction may have been secondary to reduced accessory sex organ function, which resulted in diminished secretions and fewer copulatory plugs.

Pulmonary imaging techniques in the diagnosis of occupational interstitial lung disease.

The chest radiograph is extensively used in evaluating workers at risk for developing occupational lung disease. Other pulmonary imaging techniques used in conjunction with the initial chest radiograph include conventional computed tomography, high resolution computed tomography, and gallium scintigraphy. This chapter evaluates the use of these techniques and their appropriate applications in the pneumoconioses, hypersensitivity pneumonitis, berylliosis, and hard metal diseases.

Pig Leydig cell culture: a useful in vitro test for evaluating the testicular toxicity of compounds.

In vivo studies have shown that the testis is a target organ for drugs and chemicals. In order to evaluate the testicular toxicity of compounds and to identify the mechanisms of their toxicity, we have developed a miniaturized primary culture of immature pig Leydig cells. Five well-known drugs with differing mechanisms of toxicity on testicular functions were tested to validate the model. Testosterone and progesterone secretion were measured to evaluate testicular function. Cell viability was assessed quantitatively using a colorimetric assay based on the reduction of a tetrazolium salt (3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide) which stains viable cells only, thus allowing discrimination between specific inhibitors of Leydig cell function and nonspecific cytotoxic drugs. Ketoconazole and aminoglutethimide inhibited both testosterone and progesterone secretion, but without modifying cell viability. Spironolactone specifically blocked testosterone secretion and increased progesterone concentration without inducing cell mortality. Cycloheximide altered testicular steroid secretion by another mechanism of action. Chlorpromazine, which interferes with the secretion of gonadotropins in vivo, produced a significant inhibition of progesterone and testosterone secretion as a result of the cytotoxic effects of the drug. In conclusion, this in vitro test enables one to discriminate accurately between specific and nonspecific inhibitors of steroidogenesis and could reduce the number of false positives when screening for potential testicular toxins.

Somatostatin receptors in brain and pituitary.

Somatostatin (SRIF) actions in the brain and pituitary are mediated by specific receptors. Using radioiodinated ligands it has been possible to characterize the kinetics of specific binding sites in the brain and pituitary, and to determine their cellular localization by autoradiography. At the pituitary level, the inhibition of growth hormone, prolactin and thyrotropin secretions induced by SRIF is mediated through a single binding site which is coupled to the inhibition of adenylate cyclase. In the brain, SRIF receptors are localized on neurons and glial cells and are also coupled to adenylate cyclase inhibition. Two sites are differentiated in the brain with an analogue of somatostatin, SMS 201995. In humans, SRIF-binding sites have been related to a number of pathologies. At the pituitary level, it has been shown that the number of binding sites was negatively correlated to growth hormone levels in acromegaly. Furthermore, SRIF-binding sites were undetectable in a patient which did not respond to SMS 201995 therapy. In the brain, meningiomas and gliomas are rich in SRIF binding sites. This suggests a possible role for SRIF on glia. In neurodegenerative diseases, cortical SRIF concentrations are decreased in Alzheimer's and Parkinson's disease associated with dementia while SRIF-binding sites are only affected in Alzheimer's disease. In conclusion, the physiological role of SRIF in the brain and pituitary can be evaluated by studying the receptors of the peptide. Such studies allow to question the implication of SRIF in endocrine and neuropathologies.

Differential response of lactotrophs and somatotrophs to a joint application of vasoactive intestinal Peptide and thyrotrophin-releasing hormone in the rat.

Abstract We have studied the responses of growth hormone, prolactin and thyrotrophin to vasoactive intestinal peptide and thyrotrophin-releasing hormone added either together or separately under various in vivo (free-moving, intact animals or rats bearing hypothalamic lesions) or in vitro (perifused anterior pituitary fragments) conditions. Thyrotrophin-releasing hormone or vasoactive intestinal peptide stimulated prolactin release in all cases and the individual effects of both peptides were additive when administered together. Vasoactive intestinal peptide, but not thyrotrophin-releasing hormone, induced a growth hormone response in intact rats. In contrast, both peptides stimulated growth hormone release in lesioned rats as well as in perifused anterior pituitary fragments. In that case, the effect of vasoactive intestinal peptide on growth hormone release was not additive with that of thyrotrophin-releasing hormone, either in vivo or in vitro. Thyrotrophin release was slightly stimulated by vasoactive intestinal peptide, whereas it responded markedly to thyrotrophin-releasing hormone. The effect of thyrotrophin releasing-hormone was not further affected by simultaneous vasoactive intestinal peptide administration. These data suggest that additivity of the effect of second messengers generated as a response to thyrotrophin-releasing hormone and vasoactive intestinal peptide are specific of the target cell type.

Interaction of vasoactive intestinal peptide (VIP) and growth hormone releasing factor (GRF) with corticotropin releasing factor (CRF) on corticotropin secretion in vitro.

The possible interaction of VIP and GRF with CRF on ACTH release was examined by using superfused rat anterior pituitary fragments. ACTH was measured in effluent medium samples by RIA. Increasing concentrations of VIP and GRF (10(-8) to 10(-6)M) had no effect on spontaneous ACTH secretion but potentiated CRF (10(-10)M) induced ACTH release in a dose dependent manner. The high concentrations of VIP or GRF required to produce the effect suggest that both the peptides could interfere with a common unidentified binding site on corticotrophs or stimulate a second messenger by a paracrine action.

Vasoactive intestinal peptide induces a transient release of growth hormone in the rat.

Effects of vasoactive intestinal peptide (VIP) on growth hormone (GH) secretion were investigated both in vivo on freely moving, intact or mediobasal hypothalamic lesioned rats, and in vitro in incubation or superfusion systems of anterior pituitary tissue. In vivo, IV injection of VIP induced a rapid but transient increase in plasma GH levels in all animals and in vitro, VIP stimulated GH release from incubated or superfused rat pituitaries in a concentration dependent manner. This increase was potentiated by forskolin, a potent activator of adenylate cyclase. These findings indicate that VIP exerts a direct stimulating action on somatotrophs and that the effect seems to imply a coupling of VIP receptors with cAMP production.

[Characterization of the stimulant effect of 2 neuropeptides (thyroliberin (TRH) and vasoactive intestinal peptide (VIP)) on the secretion of the growth hormone in the rat]. / Caractérisation de l'effet stimulant de deux neuro-peptides (thyréolibérine-TRH et peptide vaso-actif intestinal-VIP) sur la sécrétion de l'hormone de croissance (GH) du rat.

The effects of thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP) on growth hormone (GH) secretion were investigated in vivo in freely moving, intact or mediobasal hypothalamic-lesioned rats and in vitro in incubation or superfusion systems of anterior pituitary tissue. In vivo, the two peptides induced a rapid increase of plasma GH levels in freely moving animals, bearing an extensive lesion of the mediobasal hypothalamus including the median eminence. VIP, but not TRH, was also effective in intact animals. In vitro, TRH and VIP stimulated GH release from incubated or superfused rat pituitaries in a concentrated manner: apparent affinity was 1.22.10(-8) M for TRH and 2.5.10(-9) M for VIP. These findings indicate that TRH and VIP exert a direct stimulatory action on somatotrophs, but that the effect of TRH (not observed in freely moving, intact rats) may be modulated by still other unidentified hypothalamic neurohormones.