Transgenic and knockout mouse models for the study of luteinizing hormone and luteinizing hormone receptor function

Huhtaniemi, Ilpo; Zhang, Fu Ping; Kero, Jukka; Hämäläinen, Tuula; Poutanen, Matti

doi:10.1016/s0303-7207(01)00698-0

Cited by 37 publications

(24 citation statements)

References 40 publications

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“…Interaction of LH with its receptor has been demonstrated to be a prerequisite for normal male sexual differentiation. CG maintains pregnancy and induces male sexual development during embryonic life (Huhtaniemi et al, 2002). Until very recently it was assumed that the function of CG in adult primates was restricted to the establishment and maintenance of pregnancy.…”

Section: Primate Spermatogenesismentioning

confidence: 99%

Primate spermato gene sis: new insights into comparative testicular organisation, spermatogenic efficiency and endocrine control

Luetjens¹,

Weinbauer

Wistuba³

2005

Biological Reviews

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Owing to the close phylogenetic relationship of Platyrrhini (New World monkeys) and Catarrhini (Old World monkeys) to man, nonhuman primates are often used as models for the study of male reproductive physiology and endocrinology. This review aims at providing new data and insights into comparative primate spermatogenesis, dealing specifically with quantitative aspects of germinal epithelial organisation and germ cell production, and with the roles of gonadotrophic hormones in this process. Typically, the seminiferous epithelium is composed of specific germ cell associations (spermatogenic stages). In rodents, prosimians and most Catarrhini, tubular cross sections contain a single spermatogenic stage whereas in Platyrrhini, great apes and man multi-stage tubules are present. Since Platyrrhini represent a more basal type of primate, this spermatogenic feature must have developed convergently. The primate multi-stage tubular arrangement was previously believed to be associated with low spermatogenic efficiency. However, recent studies using new methodological approaches and comparing primate species from all taxa have revealed that multistage organisation is compatible with highly efficient spermatogenesis. In fact, meta-analysis demonstrated that the efficiency of spermatogenesis in several nonhuman primate species is comparable to that of rodents which are considered as species with highly efficient germ cell production. The duration of the spermatogenic process was not related to organisation or efficiency of spermatogenesis. Sertoli cell work load was species-specific but had no impact on germ cell numbers and on the efficiency of spermatogenesis. The gonadotrophic hormones, luteinizing hormone (LH) and follicle stimulating hormone (FSH) are the primary regulators of primate testicular function. Recent studies revealed that in New World monkeys chorionic gonadotrophin (CG)--the primate pregnancy hormone--regulates testosterone production instead of LH. Receptor studies demonstrated a dual action of the closely related hormones LH and CG in primates. It is hypothesised that following the divergence of the Platyrrhini lineage from Catarrhini, the LH/CG system evolved independently with ancestral functions of the LH/CG system retained in the neotropical taxa. In summary, key spermatogenic features are preserved across all primate taxa whereas male reproductive endocrinology features appear substantially different in the neotropical primates compared to other primate lineages.

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Section: Primate Spermatogenesismentioning

confidence: 99%

Primate spermato gene sis: new insights into comparative testicular organisation, spermatogenic efficiency and endocrine control

Luetjens¹,

Weinbauer

Wistuba³

2005

Biological Reviews

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“…The LHR is expressed predominantly in granulosa cells of the ovary and the Leydig cells of the testes. Unlike rodents [1,2], in the primate, a regular LH-LHR interaction is necessary for normal male sexual differentiation, as documented by the rare cases of LH ␤ and LHR inactivating mutations in human males [3]. In the primate, CG, produced in the trophoblast, is required for pregnancy maintenance and triggers male sexual differentiation during embryonic development.…”

Section: Introductionmentioning

confidence: 99%

A New Subclass of the Luteinizing Hormone/Chorionic Gonadotropin Receptor Lacking Exon 10 Messenger RNA in the New World Monkey (Platyrrhini) Lineage1

Gromoll

Wistuba

Terwort

et al. 2003

Biology of Reproduction

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The luteinizing hormone receptor (LHR) plays an essential role as a mediator of LH and CG action during embryonic sexual differentiation and in gametogenesis. In a hypogonadal male patient, we recently demonstrated that a genomic deletion of exon 10, located in the hinge region of the extracellular domain, results in discrimination of LH and hCG action. In the common marmoset (Calltithrix jacchus), exon 10 of the LHR is naturally missing at the mRNA level. In order to investigate whether this is an isolated species-specific phenomenon, we performed a phylogenetic screening, searching for the presence of LHR exon 10 mRNA in a number of primate species representative for the major lineages of primate evolution. The expressed LHR region encompassing exon 10 was amplified from testicular tissue by RT-PCR, cloned, and sequenced. In addition, we performed Southern blot analysis of the LHR of selected New World and Old World primates. The results revealed that exon 10 mRNA is lacking in the complete New World monkey (Platyrrhini) lineage but is present in both more primitive and more advanced primates. However, exon 10 seems to be present at the genomic level, arguing for a splicing failure possibly due to a genomic mutation or the lack of appropriate splicing factors. Considering that, in the human, LH is far less active than hCG on the LHR lacking exon 10, we addressed the question whether the existence of such a receptor has any consequences on the dual hormone LH/CG system present in Platyrrhini. Using primers specific for the known marmoset CG beta cDNA, we amplified the CG beta subunit cDNA from male common marmoset pituitaries by RT-PCR, while LH beta could not be amplified, suggesting a possible physiological role of pituitary CG in this species. In conclusion, we demonstrated for the first time that the LH mRNA without exon10 is the natural wild-type LHR in the Platyrrhini lineage. We propose that this LHR represents a new subclass of receptors that should be named LHR type II. In addition, the high expression of CG beta in the marmoset pituitary suggests a physiological role of CG in the reproductive function of these primates beyond pregnancy.

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“…Most information on gonadotropins and their receptors comes from mammalian studies, especially those using gene knockout mouse models (3)(4)(5)(6)(7)(8). These studies have shown that LH exerts its action through LHR, which is expressed in the theca cells of the ovary and Leydig cells of the testis, controlling postnatal sexual development including spermatogenesis at the round spermatid stage in males and folliculogenesis at the antral stage in females.…”

mentioning

confidence: 99%

Targeted Gene Disruption in Zebrafish Reveals Noncanonical Functions of LH Signaling in Reproduction

Chu

Liu

et al. 2014

Molecular Endocrinology

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The pivotal role of gonadotropin signaling in regulating gonadal development and functions has attracted much research attention in the past 2 decades. However, the precise physiological role of gonadotropin signaling is still largely unknown in fish. In this study, we have established both LH β-subunit (lhb) and LH receptor (lhr) knockout zebrafish lines by transcription activator-like effector nucleases. Intriguingly, both homozygous lhb and lhr mutant male fish are fertile. The fertilization rate, sperm motility, and histological structure of the testis were not affected in either lhb or lhr mutant males. On the contrary, homozygous lhb mutant females are infertile, whereas homozygous lhr mutant females are fertile. Folliculogenesis was not affected in either lhb or lhr mutants, but oocyte maturation and ovulation were disrupted in lhb mutant, whereas only ovulation was affected in lhr mutant. Differential expression of genes in the ovary involved in steroidogenesis, oocyte maturation, and ovulation was found between the lhb and lhr mutants. These data demonstrate the essential role of LH signaling in oocyte maturation and ovulation, and support the notion that LH acts through the FSH receptor in the absence of LH receptor. Moreover, the defects of lhb mutant could be partially restored by administration of human chorionic gonadotropin. This in vivo evidence in the present study demonstrates, for the first time in any vertebrate species, that LH signaling is indispensable in female reproduction but not in male reproduction. LH signaling is demonstrated to control oocyte maturation and ovulation in the ovary.

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Transgenic and knockout mouse models for the study of luteinizing hormone and luteinizing hormone receptor function

Cited by 37 publications

References 40 publications

Primate spermato gene sis: new insights into comparative testicular organisation, spermatogenic efficiency and endocrine control

Primate spermato gene sis: new insights into comparative testicular organisation, spermatogenic efficiency and endocrine control

A New Subclass of the Luteinizing Hormone/Chorionic Gonadotropin Receptor Lacking Exon 10 Messenger RNA in the New World Monkey (Platyrrhini) Lineage1

Targeted Gene Disruption in Zebrafish Reveals Noncanonical Functions of LH Signaling in Reproduction

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