Effects of Injecting Thymulin into the Anterior or Medial Hypothalamus or the Pituitary on Induced Ovulation in Prepubertal Mice

Abstract

In prepubertal mice, subcutaneous thymulin injection before equine chorionic gonadotrophin (eCG) treatment simulates ovulation; seemingly, the thymulin could be acting at the hypothalamus-pituitary axis level. Objective: This study was designed to analyze the effects of injecting thymulin into the hypothalamus or pituitary on induced ovulation of prepubertal mice. Method: Female mice, 19 days old, were anesthetized with ether and injected with saline solution or thymulin into the anterior or medial hypothalamus or the pituitary and treated with eCG when 20 days old. The ova shed were counted and serum concentrations of 17β-estradiol were measured. In the ovaries, the morphometrical analysis was performed and the atresia evaluated. Results: Ether anesthesia treatment blocked eCG-induced ovulation in almost all animals. Mice anesthetized and treated with eCG and gonadotrophin-releasing hormone (GnRH) or human chorionic gonadotrophin (hCG) ovulated a full quota of ova. Injecting saline solution into the anterior or medial hypothalamus or the pituitary did not reduce the blocking effects of ether anesthesia on induced ovulation, but the incidence of atretic follicles was higher. Injecting thymulin directly into the anterior hypothalamus did not restore ovulation, nor diminish the number of atretic follicles. In contrast, injecting thymulin into the medial hypothalamus restored the ovulation ratio and decreased the percentage of atretic follicles. Similar results were obtained by injecting thymulin into the pituitary, though thymulin treatment in the pituitary resulted in a higher number of ova shed and lower follicular atresia. Conclusion: The present results suggest that thymulin acts at the medial hypothalamus level, facilitating the release of GnRH and at the pituitary level regulating gonadotrophin release.

Thymulin gene therapy prevents the reduction in circulating gonadotropins induced by thymulin deficiency in mice

“…Consequently, the present findings strongly point to thymulin as the physiological mediator, or at least one of the mediators, of the perinatal influence of the thymus on the maturation of the pituitary-gonadal axis. This is in line with studies showing that injection of synthetic thymulin in the hypothalamus of prepubertal female mice has a facilitatory action on equine chorionic gonadotropin-induced ovulation (11). The present results also indicate that thymulin deficiency during the first 8 days of life is enough to induce low serum levels of gonadotropins as well as morphological changes at pituitary level in the adult animals.…”

Morphometric Assessment of the Impact of Serum Thymulin Immunoneutralization on Pituitary Cell Populations in Peripubertal Mice

“…Besides, production and secretion of thymulin is directly or indirectly influenced by the neuroendocrine system and there is hypophysiotropic activity [Goya et al, 2004] . Recent evidence suggests that thymulin plays a particularly relevant role in the hypothalamo-pituitary-ovarian axis in rodents [García et al, 2000;Hinojosa et al, 2004;García et al, 2005]. Interestingly, congenitally athymic (nude) mice display a number of deficiencies consistent with their lack of circulating thymic hormones (i.e.…”

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

“…), as does neonatal thymectomy. Thymulin corrects these disturbances, while in normal mice it has no effect on estrogen secretion (Goya et al, 2004;García et al, 2005). In mutant nude (athymic) mice, disturbances are observed not only in the immune system but also in the neuroendocrine and reproductive systems.…”

“…Thymic peptides, thymulin in particular, correct these disturbances (García et al, 2005). Neonatal thymulin gene therapy in nude mice results in normalization of blood thymulin and gonadotropin levels at maturity (Goya et al, 2007).…”