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Different Combinations of Regulatory Elements May Account For Expression of the Glycoprotein Hormone -Subunit Gene in Primate and Horse Placenta

Robert A. Fenstermaker^*, Todd A. Farmerie, Colin M. Clay, Debora L. Hamernik and John H. Nilson

Department of Pharmacology, Case Western Reserve University School of Medicine Cleveland, Ohio 44106

Address requests for reprints to: John H. Nilson, Ph.D., Professor, Department of Pharmacology, School of Medicine, Case Western Reserve University, 2119 Abington Road, Cleveland, OH 44106.

Abstract

Expression of the glycoprotein hormone -subunit gene occurs in the pituitaries of all mammals and in the placentas of primates and horses. In humans, tandem cAMP response elements (CREs), located in the proximal promoter-regulatory region of the -subunit gene, act together with an adjacent upstream regulatory element to confer placenta-specific expression. Here, we report that the -subunit genes of Old World Monkeys contain a single functional CRE. This suggests that tandem CREs are unique to higher primates and humans and are not absolutely required for placenta-specific expression. In contrast, the comparable promoter-regulatory region of the horse -subunit gene lacks a functional CRE but appears to retain a functional upstream regulatory element. This suggests that acquisition of placenta-specific expression of the subunit gene occurred independently in these distantly related mammals. As a result, different combinations of cis-acting elements may explain why expression of the -subunit gene only occurs in placenta of primates and horses.

FOOTNOTES

This work was supported by NIH Grants AM-28559 (to J.H.N.), HD-07138-03 (to D.L.H.), DK-0731 (to T.A.F. and R.A.F.), Cancer Research Grant P30-CA-43730, and the Ohio Edison Biotechnology Center (to J.H.N.).

^* Present address: Division of Neurosurgery, University Hospitals of Cleveland, 2074 Abington Road, Cleveland, Ohio 44106.

Recipient of a grant from the American Heart Association, Northeast Ohio Affiliate.

Received for publication June 5, 1990. Revision received July 27, 1990. Accepted for publication July 27, 1990.

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