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Prolactin (PRL) and Its Receptor: Actions, Signal Transduction Pathways and Phenotypes Observed in PRL Receptor Knockout Mice

INSERM Unité 344-Endocrinologie Moléculaire, Faculté de Médecine Necker, 75730 Paris Cedex 15, France

I. Introduction

II. PRL

A. The PRL/GH/PL family

B. PRL gene and primary structure

C. PRL tertiary structure

D. Extrapituitary PRL

III. PRL Receptor (PRLR)

A. The class 1 cytokine receptor superfamily

B. PRLR gene and primary structure

C. PRLR tertiary structure

D. PRLR binding and activation by PRL

IV. Distribution of the PRLRs

V. Biological Functions of PRL

A. Water and electrolyte balance

B. Growth and development

C. Endocrinology and metabolism

D. Brain and behavior

E. Reproduction

F. Immunoregulation and protection

G. Actions associated with pathological disease states

VI. Signal Transduction by the PRLR: Structure-Function Relationships

A. The JAK-Stat pathway

B. The Ras/Raf/MAP kinase pathway

C. Other signaling pathways

VII. Null Mutation of the PRLR Gene

A. Gene cloning, vector construction, and generation of PRLR^-/- mice

B. PRLR gene expression and PRLR protein in PRLR^-/- mice

C. Impaired mammary gland development and lactation in heterozygous females

D. Heterozygote maternal behavior

E. Homozygous females are sterile

F. Homozygous male fertility

G. Other gene-targeted mutations leading to impaired mammary gland and reproductive function

H. Other phenotypes of PRLR^-/- mice

VIII. Summary and Conclusions

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