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

Abstract

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.

Social suppression of cortisol in female marmosets: Role of luteinizing hormone/chorionic gonadotropin

“…This antibody recognizes both CG and LH; however, we refer to the results exclusively in terms of CG, in view of recent Wndings that the marmoset pituitary expresses CG but not LH and that the marmoset LH receptor may be activated preferentially by CG (Gromoll et al, 2003;Müller et al, 2004a,b). Assay sensitivity was 0.13 ng (2.67 ng/ml) at 90% binding, and intra-and inter-assay CVs of a quality-control pool assayed in quadruplicate in each assay (26% binding) were 7.5 and 9.8%, respectively.…”

“…Social groups may contain as many as six adult females, but in both the wild and captivity, only one or two behaviorally dominant females breed in each group (reviewed by French, 1997;Saltzman, 2003). Subordinate females are often anovulatory and hypoestrogenemic as a result of inhibited hypophyseal secretion of CG (Abbott et al, 1981a,b;Saltzman et al, 1998), which has been shown recently to be the major luteinizing gonadotropin secreted by the pituitary in this species and possibly other New World primates (Gromoll et al, 2003;Müller et al, 2004b). Reproductive suppression can persist for months or even years, but is reversed rapidly following separation of the subordinate female from her dominant female groupmate (Abbott and George, 1991;Abbott et al, 1988).…”

Experimental endocrine manipulation by contraceptive regimen in the male marmoset (Callithrix jacchus)

“…In order to establish the suppressive effects of NETE only and -indirectly -the impact of exogenous testosterone spermatogenesis in Callithrix jacchus -either after initial co-administration with TU or by direct use of NETE only -we added the two treatment groups in which, after TU/NETE administration, NETE only was administered (extended gestagen effect, regimen II) and one group that received NETE only (regimen III). The rationale for choosing this study design was that the regulation of male reproduction differed from that observed in old-world monkeys and great apes and is more strongly dependent on gonadotrophic action of CG (Gromoll et al 2003, Mü ller et al 2004. However, a similar picture was observed when, after initial combined TU and NETE treatment, NETE only was given subsequently.…”

“…Recently, it was shown that the reproductive endocrinology of new-world monkeys differs from oldworld monkeys, great apes and humans in terms of the gonadotrophins luteinizing hormone (LH) and CG. In the course of evolution, this hormone system has completely lost LH expression and CG has taken over all regulatory functions of LH in these monkeys (Gromoll et al 2003.…”

Blood plasma levels of anterior pituitary hormones of rabbits after apricot seed exposure in vivo

“…Anterior pituitary hormones play a key role in reproductive physiology (Bugbee et al, 1931). Gonadotropin-releasing hormone (GnRH) binds to gonadotropes to stimulate synthesis and secretion of two glycoprotein hormones: follicle stimulating hormone (FSH) and luteinizing hormone (LH) by the anterior pituitary (Gromoll et al, 2003;Müller et al, 2004a;2004b;Scammell et al, 2008). Female fertility depends on the precise execution of ovarian development, regulated allocation and maturation of oocytes, and the proliferation and differentiation of the surrounding somatic cells that occur during folliculogenesis (Elvin et al, 1998).…”