Universidad de Buenos Aires Facultad de Ciencias Veterinarias ...

The seasonal control of reproduction through the photoperiodic information relies on melatonin as the key messenger acting on the components of the hypothalamic-pituitary-gonadal axis (H.H.G.). This hormone is produced in the pineal gland by the enzyme AANAT, and binds to the MT1 and MT2 receptors o...

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Autor principal: Charif, Santiago Elias
Otros Autores: Vitullo, Alfredo Daniel
Formato: Tesis doctoral acceptedVersion
Lenguaje:Español
Publicado: Universidad de Buenos Aires. Facultad de Ciencias Veterinarias 2018
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Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=avaposgra&cl=CL1&d=HWA_2199
https://repositoriouba.sisbi.uba.ar/gsdl/collect/avaposgra/index/assoc/HWA_2199.dir/2199.PDF
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Sumario:The seasonal control of reproduction through the photoperiodic information relies on melatonin as the key messenger acting on the components of the hypothalamic-pituitary-gonadal axis (H.H.G.). This hormone is produced in the pineal gland by the enzyme AANAT, and binds to the MT1 and MT2 receptors of the hypothalamus, pituitary and ovary, where it modulates the secretion of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and the sex steroids estradiol and progesterone, respectively. The South American plains vizcacha (Lagostomus maximus) shows unique reproductive features, such as natural poliovulation of\nup to 800 oocytes per estral cycle, inhibition of follicular atresia, a prolonged pregnancy with selective embryo reabsorption and follicular recruitment, and pseudo-ovulation with generation of accesory corpora lutea accessories during pregnancy. It displays two reproductive periods\nper year, being the one from April to August more efficient than the one from October to\nFebruary. The aim of this work was to study the influence of the photoperiod on the vizcacha?s H.H.G. axis functioning. First, the mRNA sequence of hypothalamic prepro-GnRH was determined. Two isoforms that differ in the length of the 5?-UTR sequence were found. The\nGnRH variant determined was mGnRH, and showed a high degree of conservation among related caviomorphs, while the sequence of the GnRH-associated peptide (GAP) showed high variability. The analysis melatoninergic system expression throughout the reproductive cycle of the vizcacha resulted in the co-localization of GnRH with both melatonin receptors\nin hypothalamic nuclei that modulate reproduction, the preoptic area and the supraoptic and suprachiasmatic nuclei. In addition, an increase in AANAT expression and melatonin levels was determined as pregnancy progressed, and the lowest levels of hypothalamic MT1 and MT2 were registered at mid-pregnancy. This would indicate that the melatoninergic system\ncontributes to the maintenance of the extensive gestation of the vizcacha. The effect of light\navailability was determined in vizcachas at the follicular phase and at the induced luteal phase. In the first case, continuous exposure to light reduced serum levels of melatonin but increased the expression of AANAT and increased the number of antral follicles and corpora\nlutea, progesterone levels and MT2 expression in the ovary, while constant darkness increased\nGnRH and MT1 levels, serum estradiol levels and MT1 expression in the ovary. In animals at luteal phase, light increased melatonin and LH levels, while darkness stimulated the expression of AANAT and hypothalamic MT1. These results would indicate that the photoperiodic and\nhormonal imbalances differentially alter the response of the hypothalamus, pituitary and\novary depending on the stage of the estrous cycle. Hypothalamic expression of the estrogen receptors ? (RE?) and ? (RE?) also varied with light availability; at the follicular phase, an\nincrease in RE? levels was observed with light and an increase in RE? with darkness. On the other hand, in animals at luteal phase, constant light increased the hypothalamic expression of RE?. In pulsatility assays, it was observed that melatonin stimulates GnRH and LH secretion in females with induced ovulation. Also, the inhibitory effect of neurostradiol on GnRH\nsecretion was determined, while the incubation with melatonin reversed this effect. On the other hand, the joint incubation of melatonin with estradiol or with an RE? agonist increased GnRH release, suggesting that the interaction of melatonin and estradiol is necessary for the\nactivity of the H.H.G. axis In conclusion, this is the first work that shows that in the vizcacha the regulation of each organ through photoperiodic information, as well as its response to\nmelatonin and the hormonal context of the estrous cycle, converge in the modulation of the reproductive axis in a way to adjust the beginning of the activity of the H.H.G. axis with the most favorable season for reproduction. This particular regulation, dependent on the stage of\nthe estrous cycle and on the light availability, demonstrates the relevance of environmental\ninformation for carrying out a successful gestation and highlights the importance of this species as a valuable model of neuroendocrine regulation of reproduction in mammals.