Endocrinology, Vol 125, 3-12, Copyright © 1989 by Endocrine Society

ARTICLES

Neuroendocrine control of thymic hormonal production. I. Prolactin stimulates in vivo and in vitro the production of thymulin by human and murine thymic epithelial cells

M Dardenne, W Savino, MC Gagnerault, T Itoh and JF Bach
Hopital Necker, INSERM U 25, Paris, France.

The thymic epithelium is responsible for the secretion of thymic peptides, which intervene in some steps of intra- and extrathymic T cell differentiation. Recent data suggest that thymic hormone secretion is modulated by the neuroendocrine network, comprising thyroid, adrenals, and gonads. However, the role of the pituitary gland in this regulation is still poorly understood. In the present paper we studied the in vivo and in vitro influences of PRL on the secretion of thymulin, one of the chemically defined thymic hormones, by thymic epithelial cells (TEC). When injected daily (20-100 micrograms/20 g) in young or old C57BL/6 mice, PRL induced a specific increase in thymulin synthesis and secretion, respectively, measured by the number of thymulin-producing cells in the thymus and the peripheral levels of the hormone. This stimulation was dose dependent and reversible after the end of treatment. Similar findings have been made in animals with pituitary dwarfism, known to have low levels of circulating thymulin. This stimulatory effect was also observed in primary cultures of human and mouse TEC when PRL (10(-7) to 10(-8) M) was applied to culture supernatants, thus suggesting that PRL could act directly on TEC. In addition, we induced in vivo experimental hypoprolactinemia, treating mice with bromocriptine, a dopamine receptor agonist that inhibits pituitary PRL secretion. Bromocriptine treatment (100-200 micrograms/20 g) yielded a significant decrease in thymulin secretion that could be reversed by coincident treatment with PRL. In the light of previous observations that bovine GH can also increase thymulin production in aged dogs, we performed a series of experiments in vitro to evaluate whether GH has a direct effect on TEC. We observed that only human GH preparations that are known to have a PRL-like effect were efficient in stimulating thymulin biosynthesis and release into the culture supernatants. The effects of PRL on TEC were not restricted to thymic hormone production. We observed that TEC proliferation, as well as the numbers of a TEC subset defined by the expression of cytokeratins 3 and 10, could also be increased by PRL treatment. All these findings show that the pituitary gland directly affects TEC in terms of cytoskeletal and secretory protein expression as well as cell cycle.

This article has been cited by other articles:

				T. Henriques-Coelho, S. M. Oliveira, R. S. Moura, R. Roncon-Albuquerque Jr., A. L. Neves, M. Santos, C. Nogueira-Silva, F. La Fuente Carvalho, A. Brandao-Nogueira, J. Correia-Pinto, et al. Thymulin Inhibits Monocrotaline-Induced Pulmonary Hypertension Modulating Interleukin-6 Expression and Suppressing p38 Pathway Endocrinology, September 1, 2008; 149(9): 4367 - 4373. [Abstract] [Full Text] [PDF]

				E. Silva-Monteiro, L. Reis Lorenzato, O. Kenji Nihei, M. Junqueira, G. A. Rabinovich, D. K. Hsu, F.-T. Liu, W. Savino, R. Chammas, and D. M. S. Villa-Verde Altered Expression of Galectin-3 Induces Cortical Thymocyte Depletion and Premature Exit of Immature Thymocytes during Trypanosoma cruzi Infection Am. J. Pathol., February 1, 2007; 170(2): 546 - 556. [Abstract] [Full Text] [PDF]

				A. F. Muller, H. A. Drexhage, and A. Berghout Postpartum Thyroiditis and Autoimmune Thyroiditis in Women of Childbearing Age: Recent Insights and Consequences for Antenatal and Postnatal Care Endocr. Rev., October 1, 2001; 22(5): 605 - 630. [Abstract] [Full Text] [PDF]

				W. Savino and M. Dardenne Neuroendocrine Control of Thymus Physiology Endocr. Rev., August 1, 2000; 21(4): 412 - 443. [Abstract] [Full Text] [PDF]

				S E Walker, D Miller, D L Hill, and G R Komatireddy Prolactin, a pituitary hormone that modifies immune responses: Proceedings of the Mini-symposium on Prolactin and SLE, held at the 5th International Conference on Systemic Lupus Erythematosus, Cancun, Mexico Lupus, July 1, 1998; 7(6): 371 - 375. [PDF]

				C. Bole-Feysot, V. Goffin, M. Edery, N. Binart, and P. A. Kelly Prolactin (PRL) and Its Receptor: Actions, Signal Transduction Pathways and Phenotypes Observed in PRL Receptor Knockout Mice Endocr. Rev., June 1, 1998; 19(3): 225 - 268. [Abstract] [Full Text]

				R. Clark The Somatogenic Hormones and Insulin-Like Growth Factor-1: Stimulators of Lymphopoiesis and Immune Function Endocr. Rev., April 1, 1997; 18(2): 157 - 179. [Abstract] [Full Text]