Novel B219/OB receptor isoforms: Possible role of leptin in hematopoiesis and reproduction

Abstract

Hematopoietic development is a complex process that involves a large number of growth factors and cytokines. Many cytokines are known to act on more mature, lineage-restricted cells of the hematopoietic system. However, no specific factors have yet been identified that induce the expansion of the most primitive hematopoietic cells without also inducing differentiation. To search for such factors, we isolated novel cell lines from the yolk sac in order to identify genes important in early hematopoietic and endothelial development. This approach led to the discovery of B219, a sequence that is expressed in at least four isoforms in very primitive hematopoietic cell populations and which may represent a novel hemopoietin receptor. The recently published receptor for the obesity (ob) gene product (leptin) is an isoform of B219 with a nearly identical ligand binding domain. B219/obr is expressed in the yolk sac, early fetal liver, enriched hematopoietic stem cells and in a variety of lymphohematopoietic cell lines. B219/obr is also expressed at high levels in adult reproductive organs. B219/obr maps to human chromosome 1p32, a region syntenic with the recently reported location of obr on murine chromosome 4 (ref. 5).

Role of leptin in hypothalamic–pituitary function

“…From there, it is transported to the anterior lobe by the short portal vessels, which account for the remaining 30% of the blood f low to the anterior lobe. In the anterior lobe, leptin combines with ob͞ob b receptors (22) to augment both FSH and LH release and may also augment the response to LHRH.…”

“…Gonadotropin secretion is impaired and very sensitive to the negative feedback of gonadal steroids, much as in prepubertal animals (12). It has recently been shown that chronic treatment with leptin can induce recovery in the reproductive system in the ob͞ob mouse by promoting growth and function of the reproductive organs and fertility (13,14) by increasing secretion of gonadotropins (15).…”

Serum leptin levels in patients with primary hyperaldosteronism before and after treatment: relationships to insulin sensitivity

“…4 Except for the action of leptin on the food intake regulation it also plays a role in the modulation of angiogenesis, haematopoiesis, and reproduction etc. [5][6][7] Obesity is one of the well-known risk factors for arterial hypertension development. 8 Because of the clear link between obesity and the increase of serum leptin levels the relationship of serum leptin levels and blood pressure regulation was studied by a series of authors.…”

Involvement of leptin signaling in the survival and maturation of bone marrow‐derived dendritic cells

“…For example, leptin has been shown to stimulate proliferation and increase the production of a variety of cytokines in rodent T cells and monocytes/macrophages [2,[9][10][11]. In relation to the important function of leptin in immune responses, leptin receptor (Ob-R) expression has been found not only in the central nervous system but also in peripheral lymphoid tissues and hematopoietic stem cells [2,8,12]. Encoded by the diabetes (db) gene, the Ob-R is a member of the class I cytokine receptors, which have the signaling capability of IL-6-type cytokine receptors [4].…”