Partially purified thymosin fraction 5 and one of its synthetic peptide components, thymosin beta 4, but not thymosin alpha 1, stimulated secretion of luteinizing hormone--releasing factor from superfused medial basal hypothalami from random cycling female rats. In addition, luteinizing hormone was released from pituitary glands superfused in sequence with hypothalami. No release of luteinizing hormone in response to thymosin was observed from pituitaries superfused alone. These data provide the first evidence of a direct effect of the endocrine thymus on the hypothalamus and suggest a potentially important role for thymic peptides in reproductive function.

https://science.sciencemag.org/content/sci/214/4521/669.full.pdf

Thymosin stimulates secretion of luteinizing hormone-releasing factor

Neuropeptides: Conductors of the immune orchestra

Publisher Summary Monoclonal reagents have made people able to phenotypically identify four major regions of the human thymus microenvironment: the thymic capsule, interlobular septae and stroma, the subcapsular cortex, the cortex, and the medulla TE-4 + and TE-3 + thymic epithelium constitute HLA + , Ia + subsets of thymic epithelium that are candidates for cell types of the human thymic microenvironment that might participate in conferring major histocompatability complex (MHC) restriction to maturing T lymphocytes TE-4, anti-p19, and BB TECS antibodies are thymic epithelial lineage markers; they all react with the basal layer of squamous epithelium of various organs The concept that thymic epithelium is constantly differentiating in the developed thymus is suggested by the coexpression of TE-4, TE-8, TE-16, and TE-15 antigen by layers of squamous epithelial keratinocytes and by thymic epithelium Three phases of thymic microenvironment development can be defined The first phase is during early fetal development when mesodermal-derived fibrous tissue induces endodermal and ectodermal-derived thymic epithelium to proliferate and mature The second phase occurs between 9 and 15 weeks of fetal development when the thymic primordia are colonized by blood-borne thymocyte precursors Presumably during this stage, thymic epithelium promotes bone marrow cell colonization of thymus by producing chemoattractant molecules The third phase of thymic microenvironment development consists of that period of time when the thymic microenvironment contributes to various stages of intrathymic T cell functional maturation These functions involve participation in generation of the T cell repertoire, generation of MHC restriction, and the production of soluble thymotrophic factors—such as thymosinal, thymopoietin, and thymulin

The human thymic microenvironment.

Endotoxin-free thymosin fraction 5 elevated corticotropin, beta-endorphin, and cortisol in a dose- and time-dependent fashion when administered intravenously to prepubertal cynomolgus monkeys. Two synthetic component peptides of thymosin fraction 5 had no acute effects on pituitary function, suggesting that some other peptides in thymosin fraction 5 were responsible for its corticotropin-releasing activity. In agreement with these observations, total thymectomy of juvenile macaques was associated with decreases in plasma cortisol, corticotropin, and beta-endorphin. These findings indicate that the prepubertal primate thymus contains corticotropin-releasing activity that may contribute to a physiological immunoregulatory circuit between the developing immunological and pituitary-adrenal systems.

The thymus-adrenal connection: thymosin has corticotropin-releasing activity in primates

Why the neuroendocrine system is important in aging processes

The concentration of ACTH, corticosterone, LH and testosterone in the plasma of rats have been measured in normal, thymectomized and sham-operated rats. A group of rats, thymectomized at birth, received two i.p. injections weekly of two thymic extracts, each prepared in a separate way. Neonatal thymectomy was followed by the appearance of a transitory wasting disease during which a hormonal unbalance was manifest. Plasma corticosterone and ACTH levels increased at first at 30 days after thymectomy and then decreased at 60 days. The levels of the different hormones returned to normal by 90 days. The injections of thymic extracts rectified all these perturbations. The plasma levels of testosterone and corticosterone of hypophysectomized rats were compared to those of hypophysectomized and thymectomized animals. Results suggested that the thymus has a direct action of the adrenal cortex and in indirect action on the testes. The indirect effect is probably mediated through the hypophysis.

Endocrine interaction of the thymus with the hypohysis, adrenals and testes: effects of two thymic extracts.

White rats were thymectomized neonatally. After 60 days, no alteration was noted in the plasma or testis magnesium level. On the other hand, a marked decrease was observed in the magnesium content of muscle (-23%) and of bone (-19%). The injection of thymosin reversed these changes. These findings suggest that a correlation between the thymus and the muscle is exerted by a protein factor (thymosin), and that the thymus may act on sex glands through an indirect pathway.

Fontanges R

Papers

Endocrine interaction of the thymus with the hypohysis, adrenals and testes: effects of two thymic extracts.

Effect of neonatal thymectomy on the content of magnesium in the plasma and in various tissues of the rat