ABSTRACT
Xanthohumol (XH), the principal prenylflavonoid of the hop plant (Humulus lupulus L.), dose-dependently inhibited isobutylmethylxanthine (IBMX)-induced melanogenesis in B16 melanoma cells, with little cytotoxicity at the effective concentrations. Decreased melanin content was accompanied by reduced tyrosinase enzyme activity, protein and mRNA expression. The levels of tyrosinase-related protein 1 and 2 mRNAs were decreased by XH. XH also inhibited alpha-melanocyte stimulating hormone- or forskolin-induced increases in melanogenesis, suggesting an action on the cAMP-dependent melanogenic pathway. XH downregulated the protein and mRNA expression of microphthalmia-associated transcription factor (MITF), a master transcriptional regulator of key melanogenic enzymes. These results suggest that XH might act as a hypo-pigmenting agent through the downregulation of MITF in the cAMP-dependent melanogenic pathway.
Subject(s)
Animals , Mice , 1-Methyl-3-isobutylxanthine/pharmacology , Cell Line , Cell Survival/drug effects , Dose-Response Relationship, Drug , Down-Regulation , Drug Antagonism , Colforsin/pharmacology , Humulus , Intramolecular Oxidoreductases/antagonists & inhibitors , Melanins/antagonists & inhibitors , Melanocytes/drug effects , Melanoma, Experimental , Membrane Glycoproteins/antagonists & inhibitors , Microphthalmia-Associated Transcription Factor/antagonists & inhibitors , Monophenol Monooxygenase/antagonists & inhibitors , Oxidoreductases/antagonists & inhibitors , Propiophenones/pharmacology , Signal Transduction/drug effects , alpha-MSH/metabolismABSTRACT
Dada la importancia de prolactina y alfa melanotrofina en la regulación del ciclo reproductivo de mamíferos, se decidó investigar sus perfiles de secreción en el ciclo reproductivo de Columbia livia (paloma doméstica), y su comparación con las variaciones morfológicas del ovario. Se utilizaron palomas hembras en diferentes estadíos de su ciclo reproductivo: postura - incubación - cría. Las muestras ováricas se procesaron por las técnicas histológicas convencionales, mientras que los dosajes hormonales se realizaron mediante ensayo biológico para alfa-melanotrofina y radioinmunoensayo para prolactina. Se obtuvieron diferencias significativas en los distintos períodos tanto en lo que respecta a la estructura ovárica como a los valores hormonales de prolactina y alfa-melanotrofina. Ambas muestran un comportamiento similar en los respectivos estadíos del ciclo reproductor. Las concentraciones más bajas se encontraron en el período de Postura (x ñ s = 4,3 ñ 0,6; 3,5 ñ 0,26 ng/ml), aumentando significativamente en el de Incubación (x ñ s = 6,5 ñ 0,7 ng/ml; 6,6 ñ 1,7 ng/ml) y alcanzando los máximos valores en el de Cria (x ñ s = 10,33 ñ 1,8 ng/ml; 13,6 ñ 1,9 ng/ml). Concomitantemente, se observaron variaciones morfológicas en ovario con marcado desarrollo del estroma medular
Subject(s)
Female , Animals , alpha-MSH/blood , Ovary/anatomy & histology , Prolactin/blood , Reproduction , alpha-MSH/metabolism , Columbidae , Prolactin/metabolismABSTRACT
The effect of tubero-infundibular dopaminergic neurons (TIDA) on the release of prolactin (PRL) and alpha-melanocyte stimulating hormone (alpha-MSH) was studied in median eminence-lesioned (MEL) male rats (N = 6-28). Plasma PRL and alpha-MSH levels were significantly elevated 2(86.1 ñ 19.8 and 505.1 ñ 19.1 ng/ml), 4(278.7 ñ 15.5 and 487.4 ñ 125.1 ng/ml), 7 (116.2 ñ 16.2 and 495.8 ñ 62.6 ng/ml) and 14 (247.3 ñ 26.1 and 448.4 ñ 63.8 ng/ml) days after MEL when compared to sham-operated control animals (55.5 ñ 13.4 and 56.2 ñ 6.1 ng/ml, repectively). MEL altered plasma PRL and alpha-MSH levels in a diffential manner, with 1.5-to5.0-fold increase in PRL and an 8.0- to 9.0-fold increase in alpha-MSH. The increase of alpha-MSH levels occured abruptly and remained constant from days 2 to 14. These observations indicate that TIDA plays an important role in the pituitary release of PRL and alpha-MSH and provide evidence that the release of the two hormones occurs in a differential manner