The hypothalamic neuropeptide hormone GnRH is the central regulator of reproductive function. GnRH stimulates the synthesis and release of the gonadotropins LH and FSH by the gonadotropes of the anterior pituitary through activation of the G-protein-coupled GnRH receptor. In this study, we investigated the role of translational control of hormone synthesis by the GnRH receptor in the novel gonadotrope cell line LbetaT2. Using immunohistochemical and RIA studies with this model, we show that acute GnRH-induced synthesis and secretion of LH are dependent upon new protein synthesis but not new mRNA synthesis. We examined the response to GnRH and found that activation of cap-dependent translation occurs within 4 h. LHbeta promoter activity was also examined, and we found no increases in LHbeta promoter activity after 6 h of GnRH stimulation. Additionally, we show that increased phosphorylation of translation initiation proteins, 4E-binding protein 1, eukaryotic initiation factor 4E, and eukaryotic initiation factor 4G, occur in a dose- and time-dependent manner in response to GnRH stimulation. Quantitative luminescent image analysis of Western blots shows that 10 nm GnRH is sufficient to cause a maximal increase in factor phosphorylation, and maximal responses occur within 30 min of stimulation. Further, we demonstrate that the MAPK kinase inhibitor, PD 98059, abolishes the GnRH-mediated stimulation of a cap-dependent translation reporter. More specifically, we demonstrate that PD 98059 abolishes the GnRH-mediated stimulation of a downstream target of the ERK pathway, MAPK-interacting kinase. Based on these findings, we conclude that acute GnRH stimulation of LbetaT2 cells increases translation initiation through ERK signaling. This may contribute to the acute increases in LHbeta subunit production.
We present 2 patients with chronic discoid lupus erythematosus (LE) associated with xanthomatized macrophages on light microscopic findings. Skin biopsies revealed hyperkeratotic and atrophic epidermis, vacuolar degeneration of the dermal–epidermal junction, thickened basement membrane, follicular plugging, and perivascular and perifollicular lymphohistiocytic infiltrate. Notably, large collections of lipid-laden histiocytes were observed within the subjacent dermis. The patients denied history of intralesional steroid treatment. The patients did not demonstrate any clinical or laboratory signs of hyperlipidemia, cholestasis, and diabetes mellitus and insipidus. Accumulation of lipid-laden foam cells in cutaneous LE is a rare phenomenon that has been reported in discoid LE and lupus panniculitis, each only once in the literature. It has also been described within lesions of various other dermatoses in patients without lipid, hepatic, or endocrine abnormalities. Its mechanism remains unclear, but it has been hypothesized that intracellular lipids released from degenerating cells contribute to lipidization of mononuclear scavengers. Xanthomatous infiltration in cutaneous LE is an unusual feature, and its presence may not necessarily signify an underlying metabolic disorder.
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