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Notes: 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 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 stimuli. CyA seems to exert its main effects on lactotroph activity while its effects on somatotrophs and gonadotrophs are less.

Notes: The responsiveness of prolactin release to regulatory inputs depends on the functional state of the lactotrophs. In the present study, we have examined the effects of luteinizing hormone-releasing hormone (LHRH; 10–7 or 10–6 M) on the release of prolactin in vitro from hyperplastic pituitaries of estrogen-treated male Fischer rats, ectopic pituitary transplants and in situ pituitaries of grafted and control rats. The effects of dopamine (10–8 or 10–7 M) in this system were also examined. The extent of inhibition of prolactin release by dopamine was not related to the amounts of prolactin secreted under basal conditions or to plasma prolactin levels. LHRH significantly suppressed prolactin secretion in all groups but its effect was most pronounced in the ectopic pituitary transplants and in the hyperplastic pituitaries of animals after chronic exposure to estrogen followed by a period of recovery. Thus, the effects of LHRH on prolactin release appear to be related to the secretory activity and/or to the absolute or relative number of the lactotrophs.

Notes: The effect of superior cervical ganglionectomy (SCGx) on 24-h rhythms of circulating adrenocorticotropic hormone (ACTH), growth hormone (GH), prolactin and luteinizing hormone (LH) and of hypothalamic noradrenaline content and dopamine and serotonin turnover, was assessed in rats 3 days after administering Freund's complete adjuvant. In sham-operated rats, Freund's adjuvant injection increased serum ACTH without affecting its diurnal rhythmicity. SCGx, performed 10 days earlier, suppressed 24-h rhythmicity and augmented mean values of circulating ACTH. A depressive effect of immunization on GH release was found in both sham-operated and SCGx rats. GH concentrations did not exhibit diurnal rhythmicity and decreased after immunization. Time-of-day-related changes in serum prolactin were significant for all examined groups, except for SCGx-immunized rats. Freund's adjuvant administration augmented prolactin secretion. Daily changes in serum LH concentration and a decrease after immunization were found in both sham-operated and SCGx rats. SCGx: (i) counteracted inhibition of daily variations of noradrenaline content in medial hypothalamus of Freund's adjuvant-injected rats; (ii) decreased anterior hypothalamic dopamine turnover and augmented it in the medial hypothalamus; (iii) lowered amplitude of serotonin turnover rhythm in medial hypothalamus. The data indicate that several early changes in levels and 24-h rhythms of circulating ACTH and prolactin, and in hypothalamic noradrenaline content and dopamine and serotonin turnover, were modified by a previous SCGx in Freund's adjuvant-injected rats.

Notes: Wistar male rats were injected s.c. with melatonin (30 μg) or vehicle, 1 h before lights off, for 11 days. Ten days after beginning melatonin treatment, rats received Freund’s complete adjuvant or its vehicle s.c., and after 2 days, they were sacrificed at six different time intervals throughout a 24-h cycle. The mitogenic effect of lipopolysaccharide (LPS) and concanavalin A (Con A), the activity of ornithine decarboxylase (ODC) and the relative size of lymphocyte subset populations were measured in submaxillary lymph nodes. In control rats, the mitogenic effects of LPS and Con A and ODC activity peaked during the afternoon. Injection of Freund’s adjuvant induced a 10-h shift in the diurnal rhythm of the mitogenic effect of LPS to attain maximal values at night. Melatonin pretreatment blunted the daily variations in the mitogenic activity of Con A or LPS and, when given to Freund’s adjuvant-injected rats, augmented mesor and amplitude of diurnal rhythm in ODC activity. Maxima in B cell number occurred at night whereas those of T and B-T cell number occurred during the afternoon. During the early phase of immunization tested, the number of B cells augmented and the amplitude of its diurnal rhythmicity increased both after immunization and following melatonin pretreatment. Maxima of 24-h rhythms in CD4+ and CD4+/CD8+ cell populations occurred during the afternoon while those of CD8+ cells occurred at late night. Melatonin significantly augmented CD4+ cell number and decreased CD8+ cell number; it therefore augmented the CD4+:CD8+ ratio. The results suggest that pretreatment with a pharmacological dose of melatonin exerts immunomodulating effects at an early, preclinical, phase of Freund’s adjuvant-induced arthritis in rats.

Notes: Abstract This work was undertaken to assess if exposure to cadmium related to puberty may affect the episodic pattern of prolactin. Male rats were submitted to cadmium exposure, from day 30 to 60 or from day 60 to 90 of life respectively, at a dose of 50 ppm in the drinking water. Control age-matched rats received cadmium-free water. Prepubertal cadmium administration decreased mean serum prolactin levels and the absolute amplitude of the prolactin pulses. Subchronic exposure to cadmium of adult rats decreased mean serum prolactin levels, the absolute amplitude of the prolactin pulses and their duration, and the mean half-life of the hormone. These results suggest that subchronic cadmium exposure changes the secretory pattern of prolactin in adult male rats in a puberty-dependent way.

Notes: Summary Eight days after bilateral superior cervical ganglionectomy (Gx) of rats, norepinephrine content of medial basal hypothalamus (MBH) decreased significantly by 44–50%. To obtain information on other possible neurochemical sequela of Gx in MBH, we examined the metabolism of dopamine and serotonin in MBH of Gx rats by employing a high pressure liquid chromatography procedure. Eight days after Gx, MBH dopamine levels augmented significantly. Assessment of dopamine metabolism by measuring dihydroxyphenylacetic acid (DOPAC)/dopamine and homovanillic acid (HVA)/ dopamine indexes indicated a significant decrease of MBH DOPAC/dopamine ratio after Gx. MBH serotonin levels increased, and 5-hydroxyindoleacetic acid (5-HIAA)/serotonin index decreased significantly in Gx rats. To examine the interaction Gx-induced changes on MBH dopamine and serotonin with the modified hormonal milieu produced by an ectopic pituitary transplant, adult male rats bearing an ectopic pituitary within the pectoral muscles from day 5 of life were submitted to Gx on day 60 of life and were studied 8 days later. MBH dopamine content increased significantly after pituitary grafting, an effect counteracted by a subsequent Gx, while Gx alone augmented MBH dopamine levels. DOPAC and HVA contents augmented in pituitary-grafted animals, an effect counteracted by Gx. Gx increased MBH serotonin content in control but not in pituitary-grafted rats. After pituitary grafting a decrease in MBH 5-HIAA levels was found, an effect reversed by Gx. Pituitary transplants brought about a significant increase of MBH DOPAC/dopamine index, and a significant decrease in 5-HIAA/serotonin index, both effects being counteracted by Gx. Gx of control rats resulted in a significant decrease of MBH 5-HIAA/serotonin index. Analyzed as a main effect in a factorial analysis of variance, Gx decreased MBH DOPAC/dopamine and HVA/dopamine indexes significantly. Plasma prolactin increased in pituitary-grafted rats, an effect further increased by a subsequent Gx. In pituitary-grafted, Gx rats plasma GH levels augmented significantly. The data suggest that superior cervical ganglion removal affects differentially dopamine and indoleamine metabolism in MBH of control and pituitary-grafted rats.