Extragonadal LH/hCG action—Not yet time to rewrite textbooks

Abstract

Please cite this article as: Pakarainen, T., Ahtiainen, P., Zhang, F.-P., Rulli, S., Poutanen, M., Huhtaniemi, I., Extragonadal LH/hCG action -not yet time to rewrite textbooks, Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t AbstractGonadotropins are indispensable in both sexes in the regulation of gonadal sex steroid production and gametogenesis. In addition to their well established classical actions, numerous recent publications have indicated the presence and function of luteinizing hormone/chorionic gonadotropin receptors (LH/hCG-R) in a variety of extragonadal tissues. However, the physiological significance of such effects has remained unclear. We have generated two genetically modified mouse models, one with excessive production of hCG and the other with targeted disruption of LH/hCG-R gene, and used them to address the functions of LH and hCG.Numerous gonadal and extragonadal phenotypes were found in the models with the two extremes of LH/hCG action. However, when the extragonadal effects were scrutinized in greater detail, they all appeared to arise through modification of gonadal function, either through enhanced or inhibited response to LH/hCG stimulation. Hence, further evidence is needed before the extragonadal LH/hCG-R expression can be considered functionally significant.

Predictive value of bovine follicular components as markers of oocyte developmental potential

“…Similar findings have been reported in relation to gene expression in human follicular cells as predictors of pregnancy outcome post IVF, where only two genes from a panel of 10 were significantly different despite controlling for embryo quality at the outset (Hamel et al 2010). The induction of expression of the LHCGR mRNA in GC was recently identified as an early event during the follicle selection process (Luo et al 2011) and is essential for follicular maturation in the progression from antral to preovulatory stage (Pakarainen et al 2007). Follicles less than 8 mm in diameter were selected for the present study, excluding the possibility of using selected dominant follicles; therefore, granulosa cell LHCGR expression may also be reflective of follicle viability.…”

Targeted therapy for adrenocortical tumors in transgenic mice through their LH receptor by Hecate-human chorionic gonadotropin conjugate

“…Our inha/Tag TG mouse is at the moment one of the rare and unique murine models in which adrenocortical tumorigenesis and its molecular mechanisms or any treatment strategies can be investigated. Although the physiologic significances of extragonadal LHR expression in reproductive function is questioned (Pakarainen et al 2005(Pakarainen et al , 2007, some recent studies (Rao Ch et al 2004, Alevizaki et al 2006 suggest that the adrenal cortex expresses low levels of LHR (Pabon et al 1996) whose function becomes significant when LH levels are elevated, as after gonadectomy or postmenopausally. In light of the present study, we could postulate that the upregulated LHR expression in adrenal tumors is functionally relevant and can be used to target the tumors by the cytotoxic HecateCGb conjugate.…”

Molecular cloning, characterization, and expression analysis of luteinizing hormone receptor gene in turbot (Scophthalmus maximus)

“…In addition, it may also affect the follicular development by a complex signal pathway in vertebrates. LHR is also observed in extragonadal tissues, including the reproductive tract, placenta, umbilical cord, and brain, and the putative roles in these tissues are likely related to the binding of LH and hCG (Ziecik et al 1992;Pakarainen et al 2007). In teleost, LHR is found in extragonadal tissues, such as the brain, gills, kidneys, and heart (Kwok et al 2005;Maugars and Schmitz 2006;Rocha et al 2009;Ohkubo et al 2013).…”