The effects of cadmium on adrenocorticotropin hormone (ACTH) secretion are controversial and seem to depend on the dose and duration of the exposure to the metal. This work was undertaken to analyze the effects of acute cadmium administration on the episodic pattern of ACTH release in adult male rats. For this purpose, animals were cannulated 40 h before the experiment to allow a continuous blood withdrawal. Two and a half hours after the administration of a single dose of cadmium chloride (4.5 mg kg-1 bodyweight), the episodic pattern of ACTH was analyzed during three hours (from 10:30 to 13:30, samples being collected every seven minutes) in conscious and freely moving adult male rats. The mean values of ACTH during the bleeding period and the absolute pulse amplitude were decreased by acute cadmium chloride administration (P < or = 0.001, P < or = 0.01, respectively). By contrast, the frequency of ACTH pulses increased (P < or = 0.01). However, no changes in any other parameters of episodic ACTH secretion were observed compared with control animals. These data suggest that cadmium interferes with the regulatory mechanism of ACTH.

The interrelationship between the effects of prolactin and cyclosporine (CsA) appears to be very complex and until now poorly understood. The aim of the present work was to analyze whether chronic treatment with CsA could modify the episodic secretion of prolactin in male rats and whether the presence of an ectopic pituitary could counteract the effects of the drug on the pulsatile secretion pattern of this hormone. At 30 days of age, male rats were implanted with one anterior pituitary under the kidney capsule or where sham-operated. Both pituitary-grafted and sham-operated rats were injected sc for 30 days with the vehicle or CsA (5 mg/kg/day), beginning on the day of surgery. Pituitary grafting and/or CsA administration changed the pulsatile secretion pattern of prolactin. In pituitary-grafted male rats, mean serum prolactin levels, absolute pulse amplitude, and half-life of the hormone increased, while the pulse frequency decreased, compared with the values found in sham-operated rats. CsA administration to sham-operated rats increased the relative amplitude of prolactin peaks and diminished the half-life of the hormone, compared with rats of the same group treated with vehicle. However, CsA treatment in pituitary grafted rats led to lower mean serum prolactin levels and absolute amplitude, while the frequency, duration, and relative amplitude of prolactin pulses were not modified. Plasma prolactin levels did not change in control animals, whereas a reduction in circulating values of the hormone was found in pituitary grafted animals. These data suggest that CsA modifies the pulsatile secretory pattern of prolactin in pituitary-grafted male rats. The different effects observed in the control and pituitary-grafted animals might be due to a direct effect of the drug on the ectopic lactotrophs that are submitted to local regulatory influences different from those of the in situ pituitary which are submitted to the regulatory influence of the hypothalamus.

Endocrine side effects of the immunosuppressive drug cyclosporine (CyA) include changes in anterior pituitary hormone secretion. The aim of the present study was to examine the effects of CyA on the responsiveness of in situ and ectopic anterior pituitary prolactin (PRL), growth hormone (GH) and luteinizing hormone (LH) release response to dopamine (DA) and thyrotropin-releasing hormone (TRH) treatment in young female rats, and to evaluate the possible PRL participation in these effects. Thirty day old rats were rendered hyperprolactinemic by transplanting an anterior pituitary gland of a littermate donor, under the kidney capsule, and were then injected with CyA or vehicle for 2 or 8 days. Sham-operated rats were used as controls and treated in the same way. CyA treatment prevented the increase in plasma PRL levels which occurred in controls after pituitary grafting. In vitro basal PRL release of in situ pituitaries from either sham-operated and/or pituitary-grafted animals was decreased by CyA treatment at any point studied. Basal in vitro secretion of GH was only decreased in the in situ pituitaries from grafted animals after 2 days of CyA therapy. The presence of an ectopic pituitary lead to an increase in the in vitro basal LH secretion from in situ pituitaries as compared to those from sham-operated rats. Basal LH release rates were not changed by CyA treatment, although the LH release in vitro did increase in the in situ pituitaries from sham-operated animals treated with the drug for 2 days. DA addition to the incubation media decreased the in vitro release of PRL, GH and LH from the in situ pituitaries of sham-operated and pituitary-grafted animals treated with vehicle. In CyA treated animals, DA decreased in vitro PRL release from the in situ pituitaries of animals, independently of the presence or absence of an ectopic pituitary. Reductions of the in vitro GH and LH release release after DA treatment were higher in the in situ pituitaries from grafted animals on day 8 of CyA or vehicle treatment. TRH increased the in vitro release of the three hormones with differential effects related to the length of the treatment with CyA and/or the presence of an ectopic pituitary. In vitro release of PRL and GH by ectopic pituitaries was inhibited by previous treatment with CyA and this effect was decreased proportional to the duration of the treatment with the drug, while LH secretion was not modified. Addition of DA to the incubation media resulted in a marked reduction of in vitro PRL and GH release, but only at day 8 of vehicle treatment on GH release did DA addition to media further decrease the release of both hormones from ectopic pituitaries from animals treated for 2 or 8 days with the drug, whereas LH secretion was not modified. TRH addition to the incubation media of ectopic pituitaries surprisingly reduced PRL and GH secretion on day 8 of CyA treatment or after surgery. The results of these studies suggest that CyA can act directly at the hypophyseal level modifying pituitary responsiveness to external...

This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age.

Objective: To analyze the 24-hour changes in thymic and serum concentration of growth hormone (GH) and adrenocorticotropin (ACTH) and their correlation with thymic concentrations of glutamate, aspartate, taurine and GABA in young and old rats during the acute phase of adjuvant’s arthritis. Methods: Young (50-day-old) and old (18-month-old) rats were injected subcutaneously with Freund’s adjuvant or its vehicle (paraffin oil containing 15% mannide monooleate). Eighteen days later, they were killed at six different time intervals throughout a 24-hour cycle. Serum and thymic levels of GH and ACTH were measured by radioimmunoassay. Thymic amino acid concentration was measured by HPLC. A quantitative assessment of arthritis was made in an independent group of rats by plethysmography. Results: Old rats injected with Freund’s adjuvant exhibited fewer clinical signs of inflammation than young rats. Significant 24-hour changes in thymic and serum GH occurred, except for serum GH in adjuvant’s vehicle-treated old rats. Aging augmented thymic GH and decreased serum GH. Immunization with Freund’s adjuvant did not modify GH concentration. Thymic and serum concentration of GH correlated negatively. Thymic ACTH varied significantly over 24 h with maxima during the dark phase, except in Freund’s adjuvant-treated young rats. Maximal serum ACTH levels occurred in the late afternoon except in Freund’s adjuvant-treated old rats which showed maxima at night. Immunization with Freund’s adjuvant augmented thymic and circulating concentrations of ACTH. Thymic and serum concentration of ACTH correlated positively. Thymic concentration of glutamate, aspartate and taurine decreased in aged rats and correlated significantly with thymic ACTH. Conclusion: The results support the existence of a thymic compartment of GH and ACTH that may be independently regulated.