Article

Delayed Puberty and Estrogen Resistance in a Woman with Estrogen Receptor α Variant

From the Section of Reproductive Endocrinology, Infertility, and Genetics, Department of Obstetrics and Gynecology, Institute of Molecular Medicine and Genetics, and the Neuroscience Program, Medical College of Georgia, Georgia Regents University, Augusta (S.D.Q., H.-G.K., L.P.C., L.C.L.)
New England Journal of Medicine (Impact Factor: 54.42). 07/2013; 369(2):164-171. DOI: 10.1056/NEJMoa1303611
Source: PubMed

ABSTRACT Although androgen resistance has been characterized in men with a normal chromosome complement and mutations in the androgen-receptor gene, a mutation in the gene encoding estrogen receptor α (ESR1) was previously described only in one man and not, to our knowledge, in a woman. We now describe an 18-year-old woman without breast development and with markedly elevated serum levels of estrogens and bilateral multicystic ovaries. She was found to have a homozygous loss-of-function ESR1 mutation in a completely conserved residue that interferes with estrogen signaling. Her clinical presentation was similar to that in the mouse orthologue knockout. This case shows that disruption of ESR1 causes profound estrogen resistance in women. (Funded by the National Institutes of Health.).

4 Followers
 · 
185 Views
  • Nature Reviews Endocrinology 07/2013; DOI:10.1038/nrendo.2013.151 · 12.96 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Understanding the regulation of the human menstrual cycle represents an important ultimate challenge of reproductive neuroendocrine research. However, direct translation of information from laboratory animal experiments to the human is often complicated by strikingly different and unique reproductive strategies and central regulatory mechanisms that can be present in even closely related animal species. In all mammals studied so far, type-I gonadotropin releasing hormone (GnRH) synthesizing neurons form the final common output way from the hypothalamus in the neuroendocrine control of the adenohypophysis. Under various physiological and pathological conditions, hormonal and metabolic signals either regulate GnRH neurons directly or act on upstream neuronal circuitries to influence the pattern of pulsatile GnRH secretion into the hypophysial portal circulation. Neuronal afferents to GnRH cells convey important metabolic-, stress-, sex steroid-, lactational-, and circadian signals to the reproductive axis, among other effects. This article gives an overview of the available neuroanatomical literature that described the afferent regulation of human GnRH neurons by peptidergic, monoaminergic, and amino acidergic neuronal systems. Recent studies of human genetics provided evidence that central peptidergic signaling by kisspeptins and neurokinin B (NKB) play particularly important roles in puberty onset and later, in the sex steroid-dependent feedback regulation of GnRH neurons. This review article places special emphasis on the topographic distribution, sexual dimorphism, aging-dependent neuroanatomical changes, and plastic connectivity to GnRH neurons of the critically important human hypothalamic kisspeptin and NKB systems.
    Frontiers in Endocrinology 09/2013; 4:130. DOI:10.3389/fendo.2013.00130
  • New England Journal of Medicine 10/2013; 369(17):1664. DOI:10.1056/NEJMc1310364 · 54.42 Impact Factor