Abstract
Gonadotropin-releasing hormone (GnRH) and olfactory neurons migrate together in embryologic development, and disruption of this process causes idiopathic hypogonadotropic hypogonadism (IHH) with anosmia (Kallmann syndrome (KS)). Patients with IHH/KS generally manifest irreversible pubertal delay and subsequent infertility due to deficient pituitary gonadotropins or GnRH. The molecular basis of IHH/KS includes genes that: (1) regulate GnRH and olfactory neuron migration; (2) control the synthesis or secretion of GnRH; (3) disrupt GnRH action upon pituitary gonadotropes, or (4) interfere with pituitary gonadotropin synthesis or secretion. KS patients may also have midline facial defects indicating the diverse developmental functions of genes involved. Most causative genes cause either normosmic IHH or KS except FGFR1, which may cause either phenotype. Recently, several balanced chromosomal translocations have been identified in IHH/KS patients, which could lead to the identification of new disease-producing genes. Although there are two cases reported who have digenic disease, this awaits confirmation in future larger studies. The challenge will be to determine the importance of these genes in the 10-15% of couples with normal puberty who have infertility.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 165-182 |
| Number of pages | 18 |
| Journal | NeuroSignals |
| Volume | 16 |
| Issue number | 2-3 |
| DOIs | |
| State | Published - Feb 1 2008 |
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Keywords
- GnRH neuron migration
- Gonadotropin deficiency
- Gonadotropin-releasing hormone
- Hypogonadism
- Idiopathic hypogonadotropic hypogonadism
- Kallmann syndrome
- Olfactory neuron migration
ASJC Scopus subject areas
- Neurology
- Developmental Neuroscience
- Cellular and Molecular Neuroscience
Cite this
Clinical manifestations of impaired GnRH neuron development and function. / Kim, Hyung Goo; Bhagavath, Balasubramanian; Layman, Lawrence C.
In: NeuroSignals, Vol. 16, No. 2-3, 01.02.2008, p. 165-182.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Clinical manifestations of impaired GnRH neuron development and function
AU - Kim, Hyung Goo
AU - Bhagavath, Balasubramanian
AU - Layman, Lawrence C
PY - 2008/2/1
Y1 - 2008/2/1
N2 - Gonadotropin-releasing hormone (GnRH) and olfactory neurons migrate together in embryologic development, and disruption of this process causes idiopathic hypogonadotropic hypogonadism (IHH) with anosmia (Kallmann syndrome (KS)). Patients with IHH/KS generally manifest irreversible pubertal delay and subsequent infertility due to deficient pituitary gonadotropins or GnRH. The molecular basis of IHH/KS includes genes that: (1) regulate GnRH and olfactory neuron migration; (2) control the synthesis or secretion of GnRH; (3) disrupt GnRH action upon pituitary gonadotropes, or (4) interfere with pituitary gonadotropin synthesis or secretion. KS patients may also have midline facial defects indicating the diverse developmental functions of genes involved. Most causative genes cause either normosmic IHH or KS except FGFR1, which may cause either phenotype. Recently, several balanced chromosomal translocations have been identified in IHH/KS patients, which could lead to the identification of new disease-producing genes. Although there are two cases reported who have digenic disease, this awaits confirmation in future larger studies. The challenge will be to determine the importance of these genes in the 10-15% of couples with normal puberty who have infertility.
AB - Gonadotropin-releasing hormone (GnRH) and olfactory neurons migrate together in embryologic development, and disruption of this process causes idiopathic hypogonadotropic hypogonadism (IHH) with anosmia (Kallmann syndrome (KS)). Patients with IHH/KS generally manifest irreversible pubertal delay and subsequent infertility due to deficient pituitary gonadotropins or GnRH. The molecular basis of IHH/KS includes genes that: (1) regulate GnRH and olfactory neuron migration; (2) control the synthesis or secretion of GnRH; (3) disrupt GnRH action upon pituitary gonadotropes, or (4) interfere with pituitary gonadotropin synthesis or secretion. KS patients may also have midline facial defects indicating the diverse developmental functions of genes involved. Most causative genes cause either normosmic IHH or KS except FGFR1, which may cause either phenotype. Recently, several balanced chromosomal translocations have been identified in IHH/KS patients, which could lead to the identification of new disease-producing genes. Although there are two cases reported who have digenic disease, this awaits confirmation in future larger studies. The challenge will be to determine the importance of these genes in the 10-15% of couples with normal puberty who have infertility.
KW - GnRH neuron migration
KW - Gonadotropin deficiency
KW - Gonadotropin-releasing hormone
KW - Hypogonadism
KW - Idiopathic hypogonadotropic hypogonadism
KW - Kallmann syndrome
KW - Olfactory neuron migration
UR - http://www.scopus.com/inward/record.url?scp=39349113821&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=39349113821&partnerID=8YFLogxK
U2 - 10.1159/000111561
DO - 10.1159/000111561
M3 - Review article
C2 - 18253056
AN - SCOPUS:39349113821
VL - 16
SP - 165
EP - 182
JO - Neuro-Signals
JF - Neuro-Signals
SN - 1424-862X
IS - 2-3
ER -