The neuropeptide galanin is predominantly expressed by the lactotrophs (the prolactin secreting cell type) in the rodent anterior pituitary and in the median eminence and paraventricular nucleus of the hypothalamus. Prolactin and galanin colocalize in the same secretory granule, the expression of both proteins is extremely sensitive to the estrogen status of the animal. The administration of estradiol-17␤ induces pituitary hyperplasia followed by adenoma formation and causes a 3,000-fold increase in the galanin mRNA content of the lactotroph. To further study the role of galanin in prolactin release and lactotroph growth we now report the generation of mice carrying a loss-of-function mutation of the endogenous galanin gene. There is no evidence of embryonic lethality and the mutant mice grow normally. The specific endocrine abnormalities identified to date, relate to the expression of prolactin. Pituitary prolactin message levels and protein content of adult female mutant mice are reduced by 30-40% compared with wild-type controls. Mutant females fail to lactate and pups die of starvation͞dehydration unless fostered onto wild-type mothers. Prolactin secretion in mutant females is markedly reduced at 7 days postpartum compared with wild-type controls with an associated failure in mammary gland maturation. There is an almost complete abrogation of the proliferative response of the lactotroph to high doses of estrogen, with a failure to up-regulate prolactin release, STAT5 expression or to increase pituitary cell number. These data further support the hypothesis that galanin acts as a paracrine regulator of prolactin expression and as a growth factor to the lactotroph.The factors that regulate proliferation of the lactotroph are largely unknown. Further, the relationship of altered prolactin secretion to lactotroph proliferation is also unclear. Pregnancy induces a coordinated increase in prolactin release and the number of lactotrophs, with a marked involution in their number once lactation ceases (1-4). In contrast, a sustained and uncontrolled proliferation of lactotrophs culminates in the development of prolactin-secreting adenomas (prolactinomas) resulting in inappropriate lactation. The prevalence of prolactinomas is an estimated 100 per million (5). However, in autopsy series of elderly females the prevalence is 1,000-fold greater, emphasizing that most prolactinomas are clinically silent and common in the elderly population (6). Prolactinomas are also a common cause of death in female aged rats of a number of strains (7-9). Treatment of prolactinomas with dopamine agonists reduces pituitary prolactin expression and reverses lactotroph hyperplasia, emphasizing the link between prolactin expression and cellular proliferation. Prolactinomas arise as monoclonal neoplasms, indicating that one or more somatic mutations underlie tumor pathogenesis. A large and increasing body of literature has failed to identify mutations in known protooncogenes in human prolactinomas (10-12). In contrast, exogenous estro...

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We aimed to determine the importance of neutrophil activation and the source of oxidative stress in the pathogenesis of rheumatoid arthritis (RA) by quantification of advanced oxidation protein products (AOPP) and total thiol levels as markers of oxidative protein damage, malondialdehyde (MDA) levels as a marker of lipid peroxidation and myeloperoxidase (MPO) activity as a marker of neutrophil activation in patients with RA. Fifty-seven rheumatoid arthritis patients were included in the study and sub-grouped according to disease activity (active, n = 31; inactive, n = 26) and compared with healthy controls (n = 25). Serum MPO activity, AOPP, MDA, and thiol levels were measured by an enzymic spectrophotometric method. Serum MPO activity (p < 0.001), AOPP (p < 0.001), MDA (p < 0.001) and levels of thiol (p < 0.002), were higher in the patient group than the controls. Active and inactive RA groups were compared with the control group and there were significant differences between each parameter. MPO activity, AOPP, MDA and thiol levels were significantly higher in both active and inactive RA patients than the controls. On the other hand, when a comparison was made between active and the inactive stage, a statistically significant difference was present only in MDA (p < 0.05) and AOPP levels (p < 0.05). There was also a significant positive correlation between all parameters. These data strongly suggest that neutrophils, which constitute the most important source of chlorinated oxidants due to their high MPO content, may be involved in serum AOPP formation and therefore the production of a novel class of pro-inflammatory mediators of oxidative stress in RA patients and that protein oxidation could play an important role in the pathogenesis of RA as does lipid peroxidation.

Serum concentrations of magnesium, zinc and copper were measured in postmenopausal women with osteoporosis (n = 40), osteopenia (n = 40) or normal bone mineral density (n = 40) as classified on the basis of the T-score of the femur neck and dual energy X-ray absorptiometry results. Mean concentrations of magnesium and zinc were significantly lower in osteoporotic women than in both osteopenic women and normal women. In addition, magnesium and zinc concentrations in osteopenic women were significantly lower than in normal women. There were no statistically significant differences observed between the osteopenic, osteoporotic and control groups with respect to copper levels. The clinical significance of these changes needs further elucidation, but trace element supplementation, especially with magnesium and zinc and perhaps copper, may have beneficial effects on bone density.