Endocrinology, Vol 137, 4018-4026, Copyright © 1996 by Endocrine Society

ARTICLES

The ovine pars tuberalis secretes a factor(s) that regulates gene expression in both lactotropic and nonlactotropic pituitary cells

PJ Morgan, CA Webster, JG Mercer, AW Ross, DG Hazlerigg, A MacLean and P Barrett
Rowett Research Institute, Aberdeen, Scotland, United Kingdom. pjm@sari.rri.ac.uk

The purpose of this study was to determine whether the cells of the ovine pars tuberalis (PT) secrete a factor(s) that can influence the activity of cells in the pars distalis (PD). By Northern blotting of total RNA isolated from PD cells that had been stimulated in the presence of cycloheximide (10 micrograms/ml), PT cell-conditioned medium was shown to induce a significant increase in the expression of the early response gene, c-fos, above both PD cell-conditioned and nonconditioned medium control levels (P < 0.05). Although forskolin (5 microM) induced a weak increase in c-fos expression in PD cells, the effect of PT medium conditioned in the presence of forskolin enhanced this expression more than additively (P < 0.05); furthermore, this effect was reversed by melatonin. These results are consistent with the release of a factor(s) from the PT, which for simplicity we have called tuberalin. This factor was released from PT cells in a time-dependent and cycloheximide-sensitive manner and was resistant to heating at 100 C for 10 min. Tuberalin activity could be size-fractionated using molecular size cut-off filters to produce activity in both the 1- to 10- kDa and more than 10-kDa size ranges. The activities in both of these fractions were sensitive to trypsin degradation and, therefore, appeared to be peptidergic. However, it was not clarified whether the biological activities were due to one or two components. Tuberalin also induced c-fos expression in other cell types, including GH3 and NIH3T3 cells. Dual labelling of PD cells by in situ hybridization using riboprobes for c-fos and PRL demonstrated that both the less than and more than 10-kDa fractions of tuberalin activated c-fos expression in some, but not all, lactotrophs in PD cell cultures, suggesting that a primary function of the PT is to regulate the activity of lactotrophs. This was supported further by enhanced secretion of PRL from PD cells in the presence of either PT-conditioned medium or PT cells in coculture. In addition, PT-conditioned medium was found to increase c- fos in a second cell type, which did not hybridize positively for PRL, indicating the existence of other endocrine interactions between the PT and PD.

This article has been cited by other articles:

				S. M. Dupre, D. W. Burt, R. Talbot, A. Downing, D. Mouzaki, D. Waddington, B. Malpaux, J. R. E. Davis, G. A. Lincoln, and A. S. I. Loudon Identification of Melatonin-Regulated Genes in the Ovine Pituitary Pars Tuberalis, a Target Site for Seasonal Hormone Control Endocrinology, November 1, 2008; 149(11): 5527 - 5539. [Abstract] [Full Text] [PDF]

				G. C. Wagner, J. D. Johnston, I. J. Clarke, G. A. Lincoln, and D. G. Hazlerigg Redefining the Limits of Day Length Responsiveness in a Seasonal Mammal Endocrinology, January 1, 2008; 149(1): 32 - 39. [Abstract] [Full Text] [PDF]

				P. Barrett, F. J. P. Ebling, S. Schuhler, D. Wilson, A. W. Ross, A. Warner, P. Jethwa, A. Boelen, T. J. Visser, D. M. Ozanne, et al. Hypothalamic Thyroid Hormone Catabolism Acts as a Gatekeeper for the Seasonal Control of Body Weight and Reproduction Endocrinology, August 1, 2007; 148(8): 3608 - 3617. [Abstract] [Full Text] [PDF]

				P. Barrett, E. Ivanova, E S. Graham, A. W Ross, D. Wilson, H. Ple, J. G Mercer, F. J Ebling, S. Schuhler, S. M Dupre, et al. Photoperiodic regulation of cellular retinoic acid-binding protein 1, GPR50 and nestin in tanycytes of the third ventricle ependymal layer of the Siberian hamster J. Endocrinol., December 1, 2006; 191(3): 687 - 698. [Abstract] [Full Text] [PDF]

				R. Nogueiras, S. Tovar, S. E Mitchell, P. Barrett, D V. Rayner, C. Dieguez, and L. M Williams Negative energy balance and leptin regulate neuromedin-U expression in the rat pars tuberalis. J. Endocrinol., August 1, 2006; 190(2): 545 - 553. [Abstract] [Full Text] [PDF]

				J. D. Johnston, B. B. Tournier, H. Andersson, M. Masson-Pevet, G. A. Lincoln, and D. G. Hazlerigg Multiple Effects of Melatonin on Rhythmic Clock Gene Expression in the Mammalian Pars Tuberalis Endocrinology, February 1, 2006; 147(2): 959 - 965. [Abstract] [Full Text] [PDF]

				G. A. Lincoln, J. D. Johnston, H. Andersson, G. Wagner, and D. G. Hazlerigg Photorefractoriness in Mammals: Dissociating a Seasonal Timer from the Circadian-Based Photoperiod Response Endocrinology, September 1, 2005; 146(9): 3782 - 3790. [Abstract] [Full Text] [PDF]

				P. Barrett, A. W. Ross, A. Balik, P. A. Littlewood, J. G. Mercer, K. M. Moar, T. Sallmen, J. Kaslin, P. Panula, S. Schuhler, et al. Photoperiodic Regulation of Histamine H3 Receptor and VGF Messenger Ribonucleic Acid in the Arcuate Nucleus of the Siberian Hamster Endocrinology, April 1, 2005; 146(4): 1930 - 1939. [Abstract] [Full Text] [PDF]

				J. D. JOHNSTON, F. R. A. CAGAMPANG, J. A. STIRLAND, A.-J. F. CARR, M. R. H. WHITE, J. R. E. DAVIS, and A. S. I. LOUDON Evidence for an endogenous per1- and ICER-independent seasonal timer in the hamster pituitary gland FASEB J, May 1, 2003; 17(8): 810 - 815. [Abstract] [Full Text] [PDF]

				P. Klosen, C. Bienvenu, O. Demarteau, H. Dardente, H. Guerrero, P. Pevet, and M. Masson-Pevet The mt1 Melatonin Receptor and ROR{beta} Receptor Are Co-localized in Specific TSH-immunoreactive Cells in the Pars Tuberalis of the Rat Pituitary J. Histochem. Cytochem., December 1, 2002; 50(12): 1647 - 1657. [Abstract] [Full Text] [PDF]

				P. Barrett, S. Messager, C. Schuster, K. M. Moar, J. G. Mercer, and P. J. Morgan Pituitary Adenylate Cyclase-Activating Polypeptide Acts as a Paracrine Regulator of Melatonin-Responsive Cells of the Ovine Pars Tuberalis Endocrinology, June 1, 2002; 143(6): 2366 - 2375. [Abstract] [Full Text] [PDF]

				J. V. Fleming, P. Barrett, S. L. Coon, D. C. Klein, and P. J. Morgan Ovine Arylalkylamine N-Acetyltransferase in the Pineal and Pituitary Glands: Differences in Function and Regulation Endocrinology, February 1, 1999; 140(2): 972 - 978. [Abstract] [Full Text]

				A. W. Ross, C. A. Webster, M. Thompson, P. Barrett, and P. J. Morgan A Novel Interaction Between Inhibitory Melatonin Receptors and Protein Kinase C-Dependent Signal Transduction in Ovine Pars Tuberalis Cells Endocrinology, April 1, 1998; 139(4): 1723 - 1730. [Abstract] [Full Text] [PDF]

				P. Barrett, G. Davidson, D. G. Hazlerigg, M. A. Morris, A. W. Ross, and P. J. Morgan Mel 1a Melatonin Receptor Expression Is Regulated by Protein Kinase C and an Additional Pathway Addressed by the Protein Kinase C Inhibitor Ro 31-8220 in Ovine Pars Tuberalis Cells Endocrinology, January 1, 1998; 139(1): 163 - 171. [Abstract] [Full Text] [PDF]

				T. M. Bockers, J. Bockmann, A. Salem, P. Niklowitz, A. Lerchl, M. Huppertz, W. Wittkowski, and M. R. Kreutz Initial Expression of the Common {alpha}-Chain in Hypophyseal Pars Tuberalis-Specific Cells in Spontaneous Recrudescent Hamsters Endocrinology, October 1, 1997; 138(10): 4101 - 4108. [Abstract] [Full Text] [PDF]