Follicle-stimulating hormone ligand and receptor mutations, and gonadal dysfunction

被引:21
作者
Levallet, J [1 ]
Pakarinen, P [1 ]
Huhtaniemi, IT [1 ]
机构
[1] Univ Turku, Dept Physiol, Turku 20520, Finland
来源
ARCHIVES OF MEDICAL RESEARCH | 1999年 / 30卷 / 06期
关键词
follicle-stimulating hormone (FSH); follicle-stimulating hormone receptor (FSHR ); mutation; infertility; ovarian dysgenesis; G protein;
D O I
10.1016/S0188-0128(99)00058-5
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
In contrast to the general contention, infertility can be an inherited condition. Same of the genetic causes of male and female infertility have turned out to be due to inactivating mutations in the gonadotropin and gonadotropin receptor genes. The topic of the present text is to review current knowledge on mutations affecting the function of follicle-stimulating hormone (FSH). This gonadotropin, by binding to its specific G protein-coupled cell membrane receptor (FSHR), is important for normal gonadal function. Mutations affecting gonadotropin genes are extremely rare, but recent genetic studies have revealed that the pathogenesis of subfertility or infertility can be due to mutations in the FSH receptor (FSHR) gene. While mutations affecting FSHR are sporadic, polymorphism of the FSHR gene seems to be a common phenomenon. To date, six inactivating and only one activating mutation have been detected in the FSHR gene. In contrast to LHR gene, the majority of these mutations affect the extracellular domain of the receptor. Together with animal models using the transgenic and knock-out approaches, systematic analysis of alterations in the FSHR gene increases our knowledge on the structure and function of the FSHR and demonstrates that the integrity of each FSHR segment is required for proper expression of the fully active protein and for normal gonadal function. Mutations in the FSHR gene have different consequences in the reproductive function depending on the sex of the patient: while normal ovarian function is critically dependent on FSH, male fertility is possible with minimal or absent FSH action. (C) 2000 IMSS. Published by Elsevier Science Inc.
引用
收藏
页码:486 / 494
页数:9
相关论文
共 67 条
  • [1] MUTATION IN THE FOLLICLE-STIMULATING-HORMONE RECEPTOR GENE CAUSES HEREDITARY HYPERGONADOTROPIC OVARIAN FAILURE
    AITTOMAKI, K
    LUCENA, JLD
    PAKARINEN, P
    SISTONEN, P
    TAPANAINEN, J
    GROMOLL, J
    KASKIKARI, R
    SANKILA, EM
    LEHVASLAIHO, H
    ENGEL, AR
    NIESCHLAG, E
    HUHTANIEMI, I
    DELACHAPELLE, A
    [J]. CELL, 1995, 82 (06) : 959 - 968
  • [2] EXOGENOUSLY ADMINISTERED TESTOSTERONE MAINTAINS SPERMATOGENESIS QUANTITATIVELY IN ADULT-RATS ACTIVELY IMMUNIZED AGAINST GONADOTROPIN-RELEASING-HORMONE
    AWONIYI, CA
    ZIRKIN, BR
    CHANDRASHEKAR, V
    SCHLAFF, WD
    [J]. ENDOCRINOLOGY, 1992, 130 (06) : 3283 - 3288
  • [3] BAIRD DT, 1990, OVARIAN ENDOCRINOLOG, P1
  • [4] A novel phenotype related to partial loss of function mutations of the follicle stimulating hormone receptor
    Beau, I
    Touraine, P
    Meduri, G
    Gougeon, A
    Desroches, A
    Matuchansky, C
    Milgrom, E
    Kuttenn, F
    Misrahi, W
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (07) : 1352 - 1359
  • [5] AMINO-TERMINAL LEUCINE-RICH REPEATS IN GONADOTROPIN RECEPTORS DETERMINE HORMONE SELECTIVITY
    BRAUN, T
    SCHOFIELD, PR
    SPRENGEL, R
    [J]. EMBO JOURNAL, 1991, 10 (07) : 1885 - 1890
  • [6] IDENTIFICATION OF THE SITES OF N-LINKED GLYCOSYLATION ON THE FOLLICLE-STIMULATING-HORMONE (FSH) RECEPTOR AND ASSESSMENT OF THEIR ROLE IN FSH RECEPTOR FUNCTION
    DAVIS, D
    LIU, XB
    SEGALOFF, DL
    [J]. MOLECULAR ENDOCRINOLOGY, 1995, 9 (02) : 159 - 170
  • [7] Impairing follicle-stimulating hormone (FSH) signaling in vivo:: Targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance
    Dierich, A
    Sairam, MR
    Monaco, L
    Fimia, GM
    Gansmuller, A
    LeMeur, M
    Sassone-Corsi, P
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (23) : 13612 - 13617
  • [8] No evidence of a role for mutations or polymorphisms of the follicle-stimulating hormone receptor in ovarian granulosa cell tumors
    Fuller, PJ
    Verity, K
    Shen, Y
    Mamers, P
    Jobling, T
    Burger, HG
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1998, 83 (01) : 274 - 279
  • [9] Role of E box and initiator region in the expression of the rat follicle-stimulating hormone receptor
    Goetz, TL
    Lloyd, TL
    Griswold, MD
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (52) : 33317 - 33324
  • [10] THE RELATIONSHIP BETWEEN 3,5-CYCLIC ADENOSINE-MONOPHOSPHATE AND CALCIUM IN MEDIATING FOLLICLE-STIMULATING-HORMONE SIGNAL-TRANSDUCTION IN SERTOLI CELLS
    GORCZYNSKA, E
    SPALIVIERO, J
    HANDELSMAN, DJ
    [J]. ENDOCRINOLOGY, 1994, 134 (01) : 293 - 300