Neurons from Fetal Rat Brains Contain Functional Luteinizing Hormone/Chorionic Gonadotropin Receptors1

Abstract

Adult and neonatal rat brains contain functional LH/hCG receptors. These findings have led us to hypothesize that the fetal rat brain may also contain these receptors. To test this hypothesis, we isolated neurons from 19-day-old fetal rat brains and cultured them in chemically defined serum-free medium. The reverse transcription polymerase chain reaction amplified an expected 256-base pair size LH/hCG receptor fragment that could hybridize with a full-length LH/hCG receptor cDNA in Southern blotting. Northern blotting demonstrated that neurons contained a major 2.6 kilobase (kb) and a minor 4.3 kb transcript. Immunocytochemistry demonstrated that the neurons contained LH/hCG receptor immunostaining. Western immunoblotting showed that neurons contained an 80-kDa receptor protein that increased to a maximal level on Day 3 of culture and then gradually decreased until the 9th day of culture. Culturing neurons for 3 days in the presence of highly purified hCG resulted in a dose-dependent increase in the outgrowth of neurite processes and total cellular protein and a decrease in DNA fragmentation as compared to values in the corresponding controls. At the maximally effective hCG concentration, the number of neurite-bearing cells was increased by 53% and the total cellular protein by 60%, and DNA fragmentation decreased by 31%. In summary, this is the first study to demonstrate the presence of LH/hCG receptors and neurotrophic effects of hCG in fetal rat brain neurons. These findings imply that locally produced gonadotropins may possibly play a role in the growth and development of the fetal brain.

Identification and Structural Characterization of the Neuronal Luteinizing Hormone Receptor Associated with Sensory Systems

“…The smaller, M r 73,000 LHR species, on the other hand, is most likely a biosynthetic intermediate of the larger one because it contained high mannose type oligosaccharides. In contrast to these findings, Rao and co-workers (17,43,44) have previously identified a LHR form of M r 80,000 in the rat and human brain as well as in isolated rat neuronal and glial cells. This apparent discrepancy might be explained by the different methods used to detect the receptors (Western blotting versus immunoprecipitation).…”

“…This speaks for the fact that the LHR might have a role in regulation of neuronal growth and differentiation. This possibility is supported by the finding that administration of hCG has been shown to result in neurite outgrowth of cultured rat neuronal cells (44). The LHR gene was also active in distinct areas of the adult brain, indicating that the receptor might be involved in regulation of brain functions after birth as well, particularly in the sensory and autonomic systems and the hippocampal and cerebellar areas that are related to reproductive behavior, memory and motor coordination.…”

Age-dependent sexual dimorphism in cognition and stress response in the 3xTg-AD mice

“…In clinical cases, low testosterone may predispose patients to AD and there are reports that men who are genetically predisposed to acquiring AD have lower testosterone (Hogervorst et al, 2005). Furthermore, gonadotropins may influence the progression of AD pathology as these sex hormones can cross the blood brain barrier (Lukacs et al, 1995) and there is a high density of gonadotropin receptors in the hippocampus (Lei et al, 1993;Al-Hader et al, 1997b;Al-Hader et al, 1997a). Notably, there is a significant increase in luteinizing hormone in the cytoplasm of pyramidal neurons and neurofibrillary tangles of AD brains compared with age-matched controls (Bowen et al, 2002).…”

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

“…There is considerable evidence that LHR is expressed in developing and adult nervous tissue. mRNA transcripts for LHR have been shown in the brain tissue of rats, bovines, and humans (25)(26)(27)(28). Reporter genes driven by various lengths of the LHR promoter have been found to be expressed in the brain of transgenic mice (29,30).…”