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Renotropic Activity in Ovine Luteinizing Hormone Isoform(s)^*

Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical College (K.N., K.S.) Tokyo 162
Institute for Protein Research, Osaka University (S.T., F.S.) Osaka 565
the Research and Development Laboratory, Calpis Food Industry Co., Ltd. (K.O.) Tokyo 150, Japan

Address all correspondence and requests for reprints to: Dr. Kaoru Nomura, Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical College, 8–1 Kawada-cho, Shinjuku-ku, Tokyo 162, Japan.

Abstract

Renotropic activity was previously demonstrated in an ovine LH preparation. This preparation was further purified with a series of chromatographic steps, and the fractions were assayed for renotropic activity in vivo by their ability to stimulate [³H]thymidine incorporation into renal DNA of castrated hypophysectomized male rats. A purified preparation could be dissociated by acid treatment into two major constituent subunits, designated and β, each of which was composed of three microheterogeneous components (subunits ^1-3 and β_1-3) by reverse phase HPLC. Peptide mapping, including amino acid analyses and partial sequencing of the purified peptides, showed that 1) subunits ₃ and β₃ possess the full length of the polypeptide chains, with the same amino acid sequences as those of the corresponding LH subunits and β, respectively; and 2) subunits ₁ and ₂ are complexes of three polypeptides which are missing several Nterminal residues from subunit ₃. Conversely, subunits β₁ and β₂ lack the C-terminal two residues and one residue, respectively, of subunit β₃. Renotropic activity was not detected in any of the dissociated subunits alone, but association of ^1-3 with β_1-3 reconstituted the hormonal activity with different potencies. In particular, combination of subunits ₃ and β₃ (₃ · β₃) yielded a potent renotropic activity with weak gonadotropic activity. The carbohydrate composition of the purified preparation exhibiting renotropic activity differed from that of a reference oLH preparation, which possessed greater gonadotropic activity but was devoid of renotropic activity. Furthermore, renotropic activity was decreased after removal of sialic acid by treatment with neuraminidase. Thus, the oligosaccharide moieties as well as the amino acid sequences of the subunits may play an important role in the expression of renotropic activity in vivo, these effects over and above those arising from differential metabolic clearance. We conclude that pituitary renotropin represents a novel activity of a LH- isoform(s) and that the posttranslational (or the artificial, i.e. during preparation) modification of the constituent LH subunits may be responsible for modulation of renotropic activity as well as the intrinsic gonadotropic activity. (Endocrinology 123: 700–712,1988)

Footnotes

^* Portions of these studies were presented at the 9th International Congress of Nephrology, June 11–16, 1984, Los Angeles, CA; the 7th International Congress of Endocrinology, July 1–9,1984, Quebec City, Quebec, Canada; and the 69th Annual Meeting of The Endocrine Society, June 10–12,1987, Indianapolis, IN. This work was supported in part by the Foundation for Growth Science in Japan, Grants-in-Aid for General Scientific Research from the Japanese Ministry of Education, Science, and Culture (60570542 and 62570522), and the Naito Foundation Natural Science Scholarship (85–132).

Received July 21, 1987.

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