Extragonadal Luteinizing Hormone Receptors in the Reproductive Tract of Domestic Animals1

Fields, Michael J.; Shemesh, Mordechai

doi:10.1095/biolreprod.104.027201

Cited by 55 publications

(34 citation statements)

References 72 publications

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“…The pronounced upregulation of PTGFS at day 15 might be of specific importance enabling the massive burst of PGF 2a peaks. The observed cyclic upregulation of PTGS2 is linked to the upregulation of endometrial LHR (Fields & Shemesh 2004) as well as to the upregulation of ESR1/OXTR after day 12 (Asselin et al 1997b, leading to high amounts of PGH 2 provided by the rate-limiting enzyme PTGS2. The different concentrations of the distinct PG may arise from variety in number of synthases as well as the different inherent frequencies.…”

Section: Discussionmentioning

confidence: 98%

Quantitative characterization of prostaglandins in the uterus of early pregnant cattle

Ulbrich¹,

Schülke²,

Groebner³

et al. 2009

Reproduction

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Prostaglandins (PGs) are important regulators of reproductive processes including early embryonic development. We analyzed the most relevant PG in bovine uteri at different preimplantation pregnancy stages when compared with non-pregnant controls. Additionally, endometrium and trophoblast tissues were examined regarding specific enzymes and receptors involved in PG generation and function. Simmental heifers were artificially inseminated or received seminal plasma only. At days 12, 15, or 18, post-estrus uteri were flushed for PG determination by liquid chromatography-tandem mass spectrometry. Endometrium and trophoblast tissues were sampled for RNA extraction and quantitative real-time PCR analysis. At all days and points of time examined, the concentration of 6-keto PGF 1a (stable metabolite of PGI 2 ) was predominant followed by PGF 2a OPGE 2 OPGD 2 zTXB 2 (stable metabolite of TXA 2 ). At days 15 and 18, PG increased from overall low levels at day 12, with a much more pronounced increase during pregnancy. The PGF 2a /PGE 2 ratio was not influenced by status. The highest PG concentration was measured at day 15 with 6-keto PGF 1a (6.4 ng/ml) followed by PGF 2a (1.1 ng/ml) and PGE 2 (0.3 ng/ml). Minor changes in endometrial PG biosynthesis enzymes occurred due to pregnancy. Trophoblasts revealed high transcript abundance of general and specific PG synthases contributing to uterine PG. As PGI 2 and PGF 2a receptors were abundantly expressed by the trophoblast, abundant amounts of PGI 2 and PGF 2a in the uterine lumen point towards an essential role of PG for the developing embryo. High amounts of PG other than PGE 2 in the preimplantation uterus may be essential rather than detrimental for successful reproduction.

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Section: Discussionmentioning

confidence: 98%

Quantitative characterization of prostaglandins in the uterus of early pregnant cattle

Ulbrich¹,

Schülke²,

Groebner³

et al. 2009

Reproduction

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“…Even though the gonads are the main target organ for LH and hCG, numerous studies have reported the presence of LHR in multiple non-gonadal tissues (8,10). In the absence of in vivo data on their functionality, the physiological importance of these receptor sites has remained obscure.…”

Section: Discussionmentioning

confidence: 99%

“…Quite unexpectedly, a number of studies have recently reported the presence of the common LH and human chorionic gonadotropin (hCG) receptor (LHR) in a variety of extragonadal tissues, including the uterus, oviduct, cervix, placenta, mammary gland, sperm, certain areas of the brain, and many others (8)(9)(10)(11). Many of the findings were made on human tissues, but similar observations have been reported on a number of other mammalian species, including baboons, bovines, pigs, rats, and mice (9,(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Fertility in luteinizing hormone receptor-knockout mice after wild-type ovary transplantation demonstrates redundancy of extragonadal luteinizing hormone action

Pakarainen

Zhang²,

Poutanen³

et al. 2005

Journal of Clinical Investigation

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The luteinizing hormone receptor (LHR), mainly expressed in gonads, is essential for normal reproduction. However, numerous recent studies have also demonstrated LHR expression in multiple extragonadal reproductive and nonreproductive tissues. Although some effects of luteinizing hormone (LH) or its agonist, human chorionic gonadotropin, have been shown in extragonadal sites, their physiological significance remains open. In the present study, we have addressed the function of the extragonadal LHR using LHR-KO mice (LuRKO mice), in which the ovaries of prepubertal mice were orthotopically replaced with pieces of WT ovary using similarly transplanted WT mice as controls . Most ovarian transplants attained normal endocrine function in both groups of mice, as demonstrated by normal age at vaginal opening, estrous cycles, and sexual behavior. Both the LuRKO and WT mice repeatedly became pregnant (9/16 vs. 16/20 after first mating; difference not significant) and delivered similarly sized litters, which grew normally after birth, indicating normal lactation. In conclusion, fertility is restored in LuRKO mice by transplantation of WT ovarian tissue. This is achieved in the absence of extragonadal LHR expression, which indicates physiological redundancy for such receptor sites. IntroductionThe regulatory functions of the 2 gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), form the cornerstone of normal fertility. In addition to earlier studies on hypophysectomized animals, immunoneutralization of gonadotropins or gonadotropin-releasing hormone (GnRH), and treatment with GnRH analogs, more recent studies on targeted inactivation of the gonadotropin subunit and receptor genes have specifically demonstrated the need of proper function of LH, FSH, and their receptors for the maintenance of female reproduction (1-7).Quite unexpectedly, a number of studies have recently reported the presence of the common LH and human chorionic gonadotropin (hCG) receptor (LHR) in a variety of extragonadal tissues, including the uterus, oviduct, cervix, placenta, mammary gland, sperm, certain areas of the brain, and many others (8-11). Many of the findings were made on human tissues, but similar observations have been reported on a number of other mammalian species, including baboons, bovines, pigs, rats, and mice (9,(12)(13)(14)(15). On the basis of these observations, a shift in the old paradigm that gonadotropins only have gonadal actions has been proposed (8). A number of extragonadal actions for LH/hCG have been suggested, including effects on brain development and sexual behavior, regulation of

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“…Numerous recent studies have provided evidence for the expression of LH/hCG-Rs in several extragonadal tissues, thus suggesting additional non-classical actions for LH and hCG (Rao, 2001;Zhang et al, 2001b;Fields and Shemesh, 2004;Filicori et al, 2005). The novel actions suggested include improvement of blastocysts implantation (Han et al, 1999), regulation of oviduct and cervix function (Lei et al, 1993a;Lin et al, 2003), improvement of endometrial angiogenesis and growth (Filicori et al, 2005), and a role in brain development and sexual behaviour (Lei et al, 1993b;Apaja et al, 2004).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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

Pakarainen¹,

Ahtiainen²,

Zhang³

et al. 2007

Molecular and Cellular Endocrinology

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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.

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Extragonadal Luteinizing Hormone Receptors in the Reproductive Tract of Domestic Animals1

Cited by 55 publications

References 72 publications

Quantitative characterization of prostaglandins in the uterus of early pregnant cattle

Quantitative characterization of prostaglandins in the uterus of early pregnant cattle

Fertility in luteinizing hormone receptor-knockout mice after wild-type ovary transplantation demonstrates redundancy of extragonadal luteinizing hormone action

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

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