Functional Importance of Bovine Myometrial and Vascular LH Receptors and Cervical FSH Receptors

Shemesh, Mordechai; Mizrachi, Dario; Gurevich, Michael; Stram, Yehuda; Shore, Laurence S.; Fields, Michael J.

doi:10.1055/s-2001-13915

Cited by 33 publications

(39 citation statements)

References 38 publications

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“…Specific, high-affinity, low-capacity binding sites for LH/hCG were first reported in the pig myometrium (Ziecik et al, 1986(Ziecik et al, , 1992a. LH-R is also present in the myometrial muscle of women (Reshef et al, 1990), rats (Bonnamy et al, 1990;Sawitzke and Odell, 1991), rabbits (Jensen and Odell, 1988) and cows (Shemesh et al, 2001). In all of the species studied, expression of LH-R is dependent on the stage of the cycle.…”

Section: Myometriummentioning

confidence: 95%

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Actions of gonadotrophins on the uterus

Shemesh¹

2001

Reproduction

108

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The pituitary gonadotrophins, LH and FSH, in addition to hCG, belong to the family of glycoprotein hormones consisting of two dissimilar noncovalently bound α and β subunits (Pierce and Parsons, 1981). The β subunits of hCG and LH are different from those of FSH. The β subunits of LH and hCG are similar except for an additional 30 amino acids at the carboxy terminus of the β subunit of hCG. These additional amino acids are responsible for the longer half-life of hCG in the circulation compared with that of LH.The receptors (R) for both LH and FSH belong to a common gene family, the G-protein-associated seven-transmembrane domain receptors (Catt and Dufau, 1991). There is no specific receptor for hCG, which binds to the same receptor (LH-R) as pituitary LH, with a somewhat higher affinity (Huhtaniemi and Catt, 1981).The main physiological functions of the gonadotrophins are well known. LH stimulates production of androgens by theca cells in the ovary, providing a substrate for oestrogen production by granulosa cells, which triggers ovulation and provides luteotrophic activity to maintain the production of progesterone by the corpus luteum. hCG is also a luteotrophic hormone that maintains corpus luteal function until about week 9 of pregnancy, at which time the primary site of progesterone synthesis shifts to the placenta (Csapo et al., 1972). FSH stimulates follicular maturation and oestrogen production by granulosa cells in the ovary. It has became apparent over the last decade that FSH and LH, as well as GnRH, affect organs other than their 'traditional' target sites. Receptors for the gonadotrophins have been found throughout the reproductive tract: in the oviduct, myometrium, endometrium, cervix and the uterine vessels. Receptors for GnRH have been found in the endometrium and trophoblast. Various paradigms have been proposed for the function of these receptors as their expression is dynamic and changes during the oestrous cycle.The object of the present article is to review the current knowledge of extragonadal gonadotrophin receptors in the reproductive tract and to suggest the physiological functions of these receptors. It will focus on the bovine and porcine reproductive tracts, as these have been the most extensively studied, and compare data with relevant published studies in other species. Extragonadal receptors in the reproductive tract EndometriumExpression and activity of LH receptor and GnRH receptor. In the human endometrium, LH-R and GnRH-R are expressed in both epithelial and stromal cells and both receptors are expressed maximally during the luteal phase (Reshef et al., 1990; Raga et al., 1998). Comparison of immunostaining intensities revealed that human luminal and glandular epithelial cells contain more receptors than stromal, myometrial or vascular smooth muscle cells. Binding sites for LH/hCG are found in the uterus of several species, including humans. In cattle and pigs, the LH receptor, its mRNA and LH receptor protein are present in the uterus throughout the oestrous cycle, and maxim...

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Section: Myometriummentioning

confidence: 95%

“…5a) (Mizrachi and Shemesh, 1999a;Shemesh et al, 2001). Uterine tract tissues from other stages of the cycle had only a weak or no response to LH.…”

Section: Action Of Gonadotrophins On Activation Of Adenylate Cyclase mentioning

confidence: 99%

Actions of gonadotrophins on the uterus

Shemesh¹

2001

Reproduction

108

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“…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).…”

Section: Introductionmentioning

confidence: 97%

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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“…The highest concentration of LH receptors in the bovine endometrial tissue was observed on days 15-17 of the estrous cycle and declined afterwards to a nadir (Shemesh et al, 2001). Higher concentrations of LH/hCG receptors during the luteal phase (Ziecik et al, 1995), and the expression level of LHR mRNA in the uterus decreased on days 0 and 4, and increased on day 12 in guinea pigs (Jiang et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies on LHR in cattle (Sun et al, 1997;Shemesh et al 2001), pig (Ziecik, 1986;Gawronska, 1999;Wasowicz and Ziecik, 2000), goat (Shen et al, 2009), mouse (Zhang et al, 2001), rabbit, and rat (Sawitzke and Odell, 1991 ) showed that LHR is expressed in a wide variety of non-gonadal tissues and organs, such as oviduct, cervix, urinary bladder, placenta, fetal membranes, umbilical cord, brain, pineal gland, spinal cord, pituitary gland, breast, skin, adrenal gland, blood vessels in target tissues, cells of the immune system, bone, heart, stomach, spleen, kidney, muscle, liver, and intestine (Rao and Lei, 2007;Ziecik et al, 2007;Vischer and Bogerd, 2003;Kwok et al, 2005;Chen et al, 2010). In the present study, LHR mRNA and protein were detected in non-gonadal tissues from Hu sheep using real-time quantitative PCR and ELISA.…”

Section: Discussionmentioning

confidence: 99%

Expression of the luteinizing hormone receptor (LHR) gene in ovine non-gonadal tissues during estrous cycle

Wang

Zhang²,

Gao³

et al. 2012

Genet. Mol. Res.

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ABSTRACT. Luteinizing hormone (LH) is an important glycoprotein hormone that regulates gonadal function in mammals and in turn regulates physiological status changes during the estrous cycle. The function of LH is mediated by luteinizing hormone receptor (LHR). In order to examine the expression patterns of the LHR gene in non-gonadal tissues during the 4 phases of the ovine estrous cycle, tissues from healthy non-pregnant adult Hu sheep were examined according to the estrous cycle for normal ovaries using real-time fluorescence quantitative PCR and ELISA methods with GAPDH as the reference gene. LHR mRNA expression levels were significantly correlated with protein concentrations and the LHR gene was abundantly expressed in olfactory bulb, hypothalamus, rumen, small intestine, kidney, and uterine tissues. When comparing the expression levels of LHR during the 4 estrous phases in particular tissues, the results showed that LHR expression levels were significantly different and relatively lower at the estrous stage in a number of non-gonadal tissues. The trends of change in LHR expression levels were highly significantly correlated between hypothalamus and rectum, hypophysis and oviduct, ileum and 3767 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (4): 3766-3780 (2012) Expression of the LHR gene in ovine non-gonadal tissues uterus, and among jejunum, olfactory bulb, and kidney (P < 0.01), and there was also significant correlation between duodenum and oviduct, hypothalamus and medulla oblongata, jejunum and uterus, omasum and abomasum, and reticulum and colon (P < 0.05). These results indicate that the ovine LHR gene (or LH) might control important mechanisms in nongonadal tissues and that the level of LH activity in some tissues may be influenced by hormonal status during the estrous cycle.

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Functional Importance of Bovine Myometrial and Vascular LH Receptors and Cervical FSH Receptors

Cited by 33 publications

References 38 publications

Actions of gonadotrophins on the uterus

Actions of gonadotrophins on the uterus

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

Expression of the luteinizing hormone receptor (LHR) gene in ovine non-gonadal tissues during estrous cycle

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