The influence of catecholamine on the migration of gonadotropin-releasing hormone-producing neurons in the rat foetuses

Abstract

Catecholamines (CA) play an important role in the regulation of GnRH neurons in adults, and it is probable that they control GnRH-neuron development. Migration of GnRH neurons was evaluated in male and female rats at the 17th embryonic day (E17) and E21, following the daily treatment of their pregnant mothers from the 11th to the 16th and 20th day of gestation with alpha-methyl-para-tyrosine (alphaMPT), an inhibitor of catecholamine synthesis. High-performance liquid chromatography with electrochemical detection (HPLC-ED) was used to specify the alphaMPT-induced CA depletion. There was a 50-70% decrease in dopamine and noradrenaline content in the nose and in the brain of alphaMPT-treated foetuses, proving the efficacy of this pharmacological model. Immunohistochemistry was used to evaluate the percentage (%) of GnRH neurons along their migration pathway from the vomeronasal organ (VNO) in the nose to the septo-preoptic area in the forebrain which is considered as an index of neuron migration. Special attention was paid to the topographic relationships of GnRH neurons with catecholaminergic fibres. These were observed in apposition with GnRH neurons in the entrance to the forebrain. In CA-deficient foetuses, the percentage of GnRH neurons located in the rostral regions extending from the VNO to the septum was greater than in controls. However, no statistically significant difference was found in the forebrain which extended from the septum to the retrochiasmatic area. In conclusion, these data suggest that endogenous catecholamines stimulate the GnRH neuron migration in ontogenesis.

Urinary Metabolite Markers of Precocious Puberty

“…The sympathetic nervous system neurotransmitters and catecholamines, especially norepinephrine, play important roles in the regulation of GnRH neurons; therefore it is possible that they also control GnRH neuron development in ontogenesis (39,40), which is an important step in the secretion of GnRH (41).…”

Interactions Between Reproductive and Immune Systems During Ontogeny: Roles of GnRH, Sex Steroids, and Immunomediators

“…The close topographic location of GnRH-immunoreactive neurons and TH-immunoreactive nerve fibers was observed in the nucleus accumbens on days 17 and 20 and in the median eminence on day 20. A quantitative radioimmunoassay for GnRH in the caudal regions of the GnRH neuron migration route in 21-day rat fetuses showed that injection of MPT resulted in a drop of GnRH level in the anterior hypothalamus of female fetuses (Izvolskaia et al, 2009). This is additional evidence that catecholamines contribute to the regulation of development of GnRH neurons during prenatal ontogeny.…”

“…There is evidence that embryonic GnRH neurons and other topographically close neurons transiently expressing TH may also be involved in local metabolism of catecholamines. According to our data, suppression of catecholamine synthesis in rat embryos by alphamethyl-p-tyrosine ( MPT, a competitive TH inhibitor) beginning from day 11 of development leads to an increase in the number of GnRH neurons in the rostral segments of their migration route by day 17 and their accumulation in the zone of their entry into the forebrain by days 18-21 (Izvolskaia et al, 2009). Experiments with double immunohistochemical labeling allowed us to determine the regions of interaction of the catecholaminergic brain systems with migrating and differentiating GnRH neurons.…”

“…Disturbances of GnRH neuron migration caused by the absence of NCAM are responsible for the Kallmann syndrome in humans, which involves hypogonadism and anosmia. Other factors influencing the development of the GnRH system include chemoattractants and chemorepellents such as netrin, ephrin, and semaphorin 4D (Schwarting et al, 2007;Giacobini et al, 2008); neurotransmitters produced by the microenvironment of migrating GnRH neurons (GABA, serotonin, and catecholamines), which regulate the rate of their migration (Bless et al, 2000;Izvolskaia et al, 2009); and growth factors, including the fibroblast growth factor (FGF), brain-derived neurotrophic factor (BDNF), hepatocyte growth factor/scatter factor (HGF/SF), and LIF (Cronin et al, 2004;Chung et al, 2008).…”

Identification and Analysis of Two Novel Sites of Rat GnRH Receptor Gene Promoter Activity: The Pineal Gland and Retina

“…16-µm cryostat sections of brains were mounted onto slides, heated at 65°C to inhibit endogenous phosphatases, and incubated with a mixture of chromogenic enzyme substrates containing nitroblue tetrazolium and 5-bromo-4-chloro-3-indolyl phosphate (NBT/BCIP) in the appropriate buffer. Anti-GnRH rabbit polyclonal antibody (a kind gift from Dr. Tillet, Nouzilly, France) has been previously characterized [11,31,32,33]. It was used at 1/5,000 to 1/10,000 dilutions then revealed with Alexa488-conjugated secondary antibody.…”