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Comment |
Thyrostimulin, but not thyroid-stimulating hormone, acts as a paracrine regulator to activate thyroid-stimulating hormone receptor in the mammalian ovary. Sun SC et al. Thyroid-stimulating hormone receptor (TSHR), activated by either TSH or a newly discovered glycoprotein hormone thyrostimulin, plays a central role in the control of body metabolism. Interestingly, in addition to its thyroid expression, we discovered the mRNA level of THSR is periodically regulated in the rat ovary by gonadotropins. Ovarian microdissection followed by real-time PCR analysis indicated granulosa cells show the highest level of TSHR expression. Cultures of follicles and primary granulosa cells demonstrated the level of TSHR is up-regulated and dampened by the gonadotropin-driven cAMP cascade and estradiol production, respectively. Furthermore, in contrast to the negligible expression of TSH in the ovary, we also found by real-time PCR and immunohistochemical analysis that thyrostimulin is mainly expressed in oocytes. Thyrostimulin, evolving before the appearance of gonadotropins, is considered the most ancestral glycoprotein hormone. Therefore, the presence of thyrostimulin in the ovary suggests it may have a primitive function in reproduction when it activates ovarian TSHR. Next, we generated recombinant thyrostimulin protein and characterized its non-covalent heterodimeric nature. Using purified recombinant thyrostimulin, we showed the human ovarian cell line NIH:OVCAR-3 also expresses endogenous and functional TSHR. Using cultured rat granulosa cells isolated from different ovarian stages, we found that treatment with thyrostimulin increased the cAMP production and c-fos gene response significantly in the presence of gonadotropins. Thus, this study demonstrates that oocyte-derived thyrostimulin and granulosa cell-expressed TSHR comprise a novel paracrine system in the ovary, where the activity is tightly controlled by gonadotropins.
Expression of the gene for ancestral glycoprotein hormone beta subunit in the nerve cord of Amphioxus. Tando Y et al. Amphioxus belongs to the subphylum Cephalochordata, a clade of chordates phylogenetically placed at the most basal position. Despite many studies on the endocrine system of amphioxus, there were no confident lines of evidence on the presence of pituitary hormones, whereas recent amphioxus genome analyses reported that amphioxus has no pituitary hormone except for thyrostimulin, which is a glycoprotein hormone in the pituitary, brain, and other organs of vertebrates. In the present study, we cloned cDNA for one glycoprotein hormone beta subunit (GPB) from amphioxus, AmpGPB5, and phylogenetically indicated that AmpGPB5 is the ancestral molecule of glycoprotein hormone beta subunits of vertebrates including pituitary glycoprotein hormones. Synteny analyses showed conservation of chromosomal location of genes near GPB genes from amphioxus through human. The AmpGPB5 gene was expressed in a restricted region of the dorsal part of the nerve cord, glandular atrial cells of gills, and pre-vitellogenic oocytes in amphioxus. However, expression was not detected in the Hatschek's pit which is considered to be a primitive pituitary gland. On the basis of present results, we hypothesize that a portion of vertebrate pituitary hormones might be derived from an ancestral glycoprotein hormone of amphioxus that functions as a neuroendocrine hormone.
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