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Introduction Thymulin consists of a biologically inactive nonapeptide component termed FTS (an acronym for serum thymus factor in French) coupled in an equimolecular ratio to a zinc ion ( Gastinel et al . 1984 ), which confers biological activity
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The effects of thymulin administration beginning on days 19 or 24 of age on spontaneous puberty and gonadotrophin-induced ovulation were analysed in female normal and hypothymic mice. In normal and hypothymic mice, the daily administration of thymulin at 24 days of age resulted in a delay in the age of vaginal opening, with an increase in serum progesterone levels. Normal mice treated with 200 ng thymulin beginning on day 19 of age and injected with pregnant mare serum gonadotrophin (PMSG) 24 h later had an increase in ovulation rate, number of ova shed and weight of the ovaries. None of the hypothymic mice treated with thymulin on day 19 and PMSG on day 20 ovulated. PMSG treatment on day 25 induced ovulation in hypothymic mice. When these animals were injected previously with 200 ng thymulin, the number of ova shed by ovulating animals was lower than in PMSG-treated animals. Administration of thymulin and sequential injection of PMSG and human chorionic gonadotrophin 54 h later resulted in an increase in ovulatory response in comparison with those receiving only PMSG. The results suggest that thymulin plays a role in the regulation of spontaneous puberty through its effects on adrenal and ovarian endocrine functions. The increase in the ovarian PMSG response-treated animals, previously given thymulin, showed that this thymic hormone participates in the regulation of gonadotrophin secretion mechanisms and seems to be dose- and age-dependent. In hypothymic mice, neuroendocrine mechanisms regulating puberty are different from those of normal mice.
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The effects of thymectomy performed on 10-day-old (Tx-10) mice on spontaneous puberty and the ovulatory response induced by gonadotrophin treatment were analysed, together with the effects of thymulin replacement from 10 days of age. Infantile thymectomy induced a delay of puberty, a decrease in serum 17beta-oestradiol concentration and a reduced total number of follicles. Injection of thymulin (12 ng/g body weight) to Tx-10 mice resulted in an earlier onset of puberty, a decrease in the weights of ovaries and uterus, and an increase in serum 17beta-oestradiol concentrations. In control and Tx-10 mice, treatment with pregnant mare serum gonadotrophin (PMSG) (5 IU) at 25 days of age resulted in ovulation and the numbers of ova shed by ovulating animals were similar. When the animals were injected with 1 IU PMSG ovulation did not occur. In Tx-10 mice, both 1 and 5 IU PMSG increased the number of follicles to values similar to those observed in the controls. In Tx-10 mice the sequential injection of PMSG (1 IU) and human chorionic gonadotrophin (hCG) (3 IU) resulted in ovulation, but the number of ova shed was lower than in controls. When these animals were injected daily with thymulin, an increase in the number of ova shed and serum 17beta-oestradiol concentrations was observed. The uterine weight of Tx-10 mice was always significantly reduced in response to gonadotrophin treatment. Thymulin injection in PMSG-hCG-treated Tx-10 mice provoked a significant increase in uterine weight. The results suggest that the presence of the thymus after the neonatal period is necessary to normal ovarian development and function. The increase in gonadotrophin-induced ovarian response produced by thymulin replacement indicates that this peptide has a role in this process as one of the connecting signals between thymus and ovaries.
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Introduction
Communication between the neuroendocrine and immune systems is crucial to host defence in both health and disease for it provides a humoral means whereby the central nervous system may fine tune the immune system and thereby bring to bear the influence of a variety of physical, emotional and environmental factors. In the past decade, several lines of communication between the two systems have been identified. These include direct autonomic innervation of lymphoid tissues and humoral factors derived from immune cells (e.g. cytokines, eicosanoids, peptides) and peripheral endocrine glands (e.g. peptides, steroids). Central to this complex interplay are the thymic hormones, a heterogeneous family of polypeptides produced by the thymic epithelium whose members include thymosin α1, thymosin β4, thymopoietin, thymulin, MB-35 and a number of less well-characterized peptides (Table 1). These peptides possess a spectrum of immunoregulatory properties. In addition, they provide the basis of a significant humoral
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38 – 45 . ( doi:10.1016/j.mce.2008.01.007 ) Land SC Darakhshan F 2004 Thymulin evokes IL-6-C/EBPβ regenerative repair and TNF-α silencing during endotoxin exposure in fetal lung explants . American Journal of Physiology. Lung Cellular and