I have often wondered what "other" effects LH/HCG has besides what we've identified in the testes. Is this the missing component of libido or completing the sense of well-being? No idea....just wondering.
You can find research out there that shows extragonadal LH receptors found in rat penis as well as other tissues.......just took a quick look. Certainly if someone is well-read in this area please contribute.
There is nothing at this time that would support the use of hCG for anything other than the testes effect. Considering the length of time that has passed and the very very few studies published in this area, I do not hold out much for a direct LH/hCG central effect.
Lei ZM, Rao CV, Kornyei JL, Licht P, Hiatt ES. Novel expression of human chorionic gonadotropin/luteinizing hormone receptor gene in brain. Endocrinology 1993;132(5):2262-70. Novel expression of human chorionic gonadotropin/luteinizing hormone receptor gene in brain.
LH from anterior pituitary and hCG from placenta bind to a common receptor in gonadal and nongonadal reproductive tissues. There have been numerous examples suggesting that the brain may also contain hCG/LH receptors, yet there has been no evidence for their existence so far. We now demonstrate by reverse transcription-nested polymerase chain reaction and northern blotting that the rat brain contains hCG/LH receptor mRNA. A major receptor transcript of 2.6 kilobases and minor transcripts of 1.8 and 4.4 kilobases were found. Western immunoblotting, ligand blotting, and covalent receptor cross-linking studies have shown that rat brain also contains an 80-kilodalton receptor protein that can bind hCG and hLH, but not hFSH. Rat testis used as a positive control showed a higher abundance of multiple transcripts and an 80-kilodalton receptor protein that can bind [125I]hCG. Rat liver used as a negative control did not contain any receptor transcripts or protein. In situ hybridization, dot blotting, immunocytochemistry, and topical autoradiography have revealed that hCG/LH receptors are present in rat hippocampus; dentate gyrus; hypothalamus; cerebellum; choroid plexus; ependymal cells of third, fourth, and lateral ventricles; cortex; brainstem; bovine hypothalamus; and human area postrema. These novel findings could potentially explain numerous previous observations and suggest new possibilities concerning the regulation of brain functions by hCG and LH.
Webber KM, Perry G, Smith MA, Casadesus G. The Contribution of Luteinizing Hormone to Alzheimer Disease Pathogenesis. CLINICAL MEDICINE & RESEARCH 2007;5(3):177-83. The Contribution of Luteinizing Hormone to Alzheimer Disease Pathogenesis
Several hypotheses have been proposed that attempt to explain the pathogenesis of Alzheimer Disease (AD) including theories involving senile plaque and neurofibrillary tangle formation, increased oxidative stress, and cell cycle abnormalities, since evidence for each of these pathological phenomena have been well documented in AD. Recent epidemiological and experimental data also support a role for the gonadotropin luteinizing hormone in AD. Paralleling the female predominance for developing AD, luteinizing hormone levels are significantly higher in females as compared to males, and furthermore, luteinizing hormone levels are higher still in individuals who succumb to AD. Luteinizing hormone, which is capable of modulating cognitive behavior, is not only present in the brain, but also has the highest receptor levels in the hippocampus, a key processor of cognition that is severely deteriorated in AD. Furthermore, we recently examined cognitive performance in a well-characterized transgenic mouse that over-expresses luteinizing hormone and found that these animals show decreased cognitive performance when compared to controls. We have also found that abolishing luteinizing hormone in amyloid-{beta} protein precursor transgenic mice (Tg2576) using a potent gonadotropin-lowering gonadotropin-releasing hormone agonist, leuprolide acetate, resulted in improved hippocampally-related cognitive performance and decreased amyloid-{beta} deposition. These findings, together with data indicating that luteinizing hormone modulates amyloid-{beta} protein precursor processing in vivo and in vitro, suggest that luteinizing hormone may contribute to AD pathology through an amyloid-dependent mechanism. These promising findings support the importance of luteinizing hormone in AD and bring to the forefront an alternative, and much needed, therapeutic avenue for the treatment of this insidious disease.
Yang E-J, Nasipak BT, Kelley DB. Direct action of gonadotropin in brain integrates behavioral and reproductive functions. Proceedings of the National Academy of Sciences 2007;104(7):2477-82. Direct action of gonadotropin in brain integrates behavioral and reproductive functions
Essential roles for gonadotropins in gonadal development and reproduction are well established. Over the past decade, however, the expression of luteinizing hormone receptor (LHR) has also been reported in the brain of various mammals and birds. Although suggestive, it has not yet been determined whether this expression pattern supports a novel function for gonadotropins. Here, we demonstrate a CNS-mediated role of gonadotropins in a reproductive behavior: the courtship songs of the South African clawed frog, Xenopus laevis. Male advertisement calling in this species depends on a nongonadal action of gonadotropin. To determine whether this effect is due to action on the CNS, we administered gonadotropin intracerebroventricularly (ICV) or systemically to intact or castrated males with or without concomitant androgen replacement. In intact and androgen-replaced gonadectomized males, gonadotropin significantly increased calling within 1 h after ICV injection. The effective dosage via ICV injections was less than one hundredth of the effective systemic dose. In situ hybridization with a cloned fragment of Xenopus LHR revealed strong expression in ventral forebrain areas important for vocal control. Further, gonadotropin treatment of brain in vitro up-regulates immunoreactivity for the LHR downstream target, egr-1, specifically in these vocal forebrain areas. Up-regulation occurs even when synaptic transmission is suppressed by incubation in Ca2+ free/high magnesium saline. These results demonstrate a neural role for gonadotropin in the control of calling behavior, potentially mediated via LHRs in forebrain vocal nuclei. Gonadotropin may play a novel integrative role in modulating both reproductive physiology and behavior.
Rahman NA, Rao CV. Recent progress in luteinizing hormone/human chorionic gonadotrophin hormone research. Molecular Human Reproduction 2009;15(11):703-11. Recent progress in luteinizing hormone/human chorionic gonadotrophin hormone research
The role of luteinizing hormone (LH) and human chorionic gonadotrophin hormone (hCG) in the regulation of normal reproductive functions in males and females is quite well established. Besides the use of hCG in the development of diagnostic immunoassays, it has been successfully used in the induction of final follicular maturation and ovulation in the assisted reproductive technologies. The basic and clinical research on the nongonadal actions of LH/hCG in the recent years has extended the potential of using these hormones in several clinical indications. Hereby we will analyze the advances in the LH/hCG research (briefly emphasizing the nongonadal research), which has the potential for multiple novel therapies in reproductive and the other areas of medicine.
Krsmanovic LZ, Martinez-Fuentes AJ, Arora KK, et al. Autocrine Regulation of Gonadotropin-Releasing Hormone Secretion in Cultured Hypothalamic Neurons. Endocrinology 1999;140(3):1423-31. http://endo.endojournals.org/content/140/3/1423.full
Episodic hormone secretion is a characteristic feature of the hypothalamo-pituitary-gonadal system, in which the profile of gonadotropin release from pituitary gonadotrophs reflects the pulsatile secretory activity of GnRH-producing neurons in the hypothalamus. Pulsatile release of GnRH is also evident in vitro during perifusion of immortalized GnRH neurons (GT1–7 cells) and cultured fetal hypothalamic cells, which continue to produce bioactive GnRH for up to 2 months. Such cultures, as well as hypothalamic tissue from adult rats, express GnRH receptors as evidenced by the presence of high-affinity GnRH binding sites and GnRH receptor transcripts. Furthermore, individual GnRH neurons coexpress GnRH and GnRH receptors as revealed by double immunostaining of hypothalamic cultures. In static cultures of hypothalamic neurons and GT1–7 cells, treatment with the GnRH receptor antagonist, [D-pGlu1, D-Phe2, D-Trp3,6]GnRH caused a prominent increase in GnRH release. In perifused hypothalamic cells and GT1–7 cells, treatment with the GnRH receptor agonist, des-Gly10-[D-Ala6]GnRHN-ethylamide, reduced the frequency and increased the amplitude of pulsatile GnRH release, as previously observed in GT1–7 cells. In contrast, exposure to the GnRH antagonist analogs abolished pulsatile secretion and caused a sustained and progressive increase in GnRH release. These findings have demonstrated that GnRH receptors are expressed in hypothalamic GnRH neurons, and that receptor activation is required for pulsatile GnRH release in vitro. The effects of GnRH agonist and antagonist analogs on neuropeptide release are consistent with the operation of an ultrashort-loop autocrine feedback mechanism that exerts both positive and negative actions that are necessary for the integrated control of GnRH secretion from the hypothalamus.
Kokk K, Kuuslahti M, Keisala T, et al. Expression of LH Receptors in the Mouse Penis. J Androl:jandrol.109.008623. Expression of LH Receptors in the Mouse Penis -- Kokk et al., 10.2164/jandrol.109.008623 -- Journal of Andrology
The role of luteinizing hormone (LH) in the regulation of normal reproductive functions in males and females is quite well established. Besides the expression of LH receptors in the target cells in gonads, it has been found in several extragonadal organs. There is no information about the expression of LH receptors in the penis up to now. The aim of present study is to investigate the expression of LH receptor in the mouse penis to see if LH effects are possible in the penis. BALB/c mice were used as donors of normal penis and testis tissue. Immunocytochemistry, Western blotting and quantitative RT-PCR reactions were used for the detection of the LH receptor. Positive immunoreaction for LH receptors was present in the nuclei of urethral epithelium and endothelial cells of cavernous spaces in the corpus cavernosum and corpus spongiosum penis. Western blotting experiments demonstrated the presence of LH antigen at Mr = 97.4 and 78 kD. Quantitative RT- PCR reactions confirmed the expression of LH receptor in the penis. Our results show that LH receptor is expressed in the body of the mouse penis, thus it may directly regulate functions of penile tissue.
