Gonadotropin-Releasing Hormone Deficiency in the Human (Idiopathic Hypogonadotropic Hypogonadism and Kallmanns Syndrome): Pathophysiological and Genetic Considerations
Stephanie B. Seminara1,
Frances J. Hayes1 and
William F. Crowley, Jr.
Reproductive Endocrine Unit of the Department of Medicine and the
National Center for Infertility Research, Massachusetts General
Hospital, Boston, Massachusetts 02114
I. Introduction
II. Ontogeny of Normal GnRH Secretion
A.Fetal life
B. Neonatal and childhood periods
C. Puberty
D. Adulthood
III. Historical Perspective
IV. ClinicalPresentation of GnRH Deficiency
A. Congenital GnRH deficiency
B. Adult-onset GnRH deficiency
C. Variant or partial formsof GnRH deficiency
D. Associated anomalies in KS
E. Differentialdiagnosis
V. Approaches to Studying GnRH Secretion
A. Animaland in vitro studies
B. Human studies
VI. Patterns of GnRHSecretion in Men with GnRH Deficiency
VII. Patterns of GnRHSecretion in Women with GnRH Deficiency
VIII. Genetic Studies
IX. X-Linked Genes Controlling GnRH Secretion
A. Kallmannssyndrome gene
B. Adrenal hypoplasia congenita (AHC) gene product
X. Autosomal Genes Controlling GnRH Secretion
A. The geneticsof autosomal inheritance
B. GnRH gene
C. GnRH receptor gene
D. Other autosomal genes
XI. Conclusion
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