KiSS-1 in the mammalian ovary: distribution of kisspeptin in human and marmoset and alterations in KiSS-1 mRNA levels in a rat model of ovulatory dysfunction
| Autor: | Robert P. Millar, Juan Carlos Roa, Juan M. Castellano, Hamish M. Fraser, Manuel Tena-Sempere, Nicolás Garrido, M. Romero, Francisco Gaytan, Belén Aparicio, José E. Sánchez-Criado, María Gaytán, Antonio Pellicer |
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| Rok vydání: | 2009 |
| Předmět: |
endocrine system
medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism media_common.quotation_subject Indomethacin Gene Expression Biology Dinoprostone Receptors G-Protein-Coupled Kisspeptin Kisspeptins Physiology (medical) Internal medicine biology.animal Follicular phase Progesterone receptor medicine Animals Humans Cyclooxygenase Inhibitors Ovarian Diseases RNA Messenger Rats Wistar Receptor Ovulation media_common Mammals Reverse Transcriptase Polymerase Chain Reaction Tumor Suppressor Proteins Ovary Proteins Marmoset Callithrix Rats Disease Models Animal Tocolytic Agents Endocrinology Theca Female human activities hormones hormone substitutes and hormone antagonists Receptors Kisspeptin-1 |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 296:E520-E531 |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.90895.2008 |
| Popis: | Kisspeptins, the products of the KiSS-1 gene acting via G protein-coupled receptor 54 (GPR54), have recently emerged as pivotal signals in the hypothalamic network triggering the preovulatory surge of gonadotropins and, hence, ovulation. Additional actions of kisspeptins at other levels of the hypothalamic-pituitary-ovarian axis have been suggested but remain to date scarcely studied. We report herein the pattern of expression of KiSS-1 and GPR54 in the human and nonhuman primate ovary and evaluate changes in ovarian KiSS-1 expression in a rat model of ovulatory dysfunction. KiSS-1 and GPR54 mRNAs were detected in human ovarian tissue and cultured granulosa-lutein cells. In good agreement, kisspeptin immunoreactivity was observed in cyclic human and marmoset ovaries, with prominent signals in the theca layer of growing follicles, corpora lutea, interstitial gland, and ovarian surface epithelium. GPR54 immunoreactivity was also found in human theca and luteal cells. Administration of indomethacin to cyclic female rats disturbed ovulation and resulted in a dramatic drop in ovarian KiSS-1, but not GPR54, cyclooxygenase-2 (COX-2), or progesterone receptor, mRNA levels at the time of ovulation; an effect mimicked by the selective COX-2 inhibitor NS398 and rescued by coadministration of PGE2. Likewise, the stimulatory effect of human choriogonadotropin on ovarian KiSS-1 expression was partially blunted by indomethacin. In contrast, KiSS-1 mRNA levels remained unaltered in another model of ovulatory failure, i.e., the RU486-treated rat. In summary, we document for the first time the expression of KiSS-1/kisspeptin and GPR54 in the human and nonhuman primate ovary. In addition, we provide evidence for the ability of inhibitors of COX-2, known to disturb follicular rupture and ovulation, to selectively alter the expression of KiSS-1 gene in rat ovary. Altogether, our results are suggestive of a conserved role of local KiSS-1 in the direct control of ovarian functions in mammals. |
| Databáze: | OpenAIRE |
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