The Experts below are selected from a list of 879 Experts worldwide ranked by ideXlab platform

Ram M Sairam - One of the best experts on this subject based on the ideXlab platform.

  • Printed in U.S.A. Copyright © 2001 by The Endocrine Society Ovarian Pathology and High Incidence of Sex Cord Tumors in Follitropin Receptor Knockout (FORKO) Mice
    2013
    Co-Authors: Natalia Danilovich, Indrojit Roy, Ram M Sairam
    Abstract:

    In this investigation we describe our observations of the status of the aging ovary in mice with disruption of the receptor for FSH. Knockout mice at 3–5 months of age are acyclic and sterile, with very small, underdeveloped ovaries. Thus, they exhibit Hypergonadotropic-Hypogonadism with high levels of circulating FSH similar to the postmenopausal state in women. By 12 months more than 92 % of these animals developed various kinds of ovarian pathology, including neoplasms of sex cord-stromal type as well as cysts. Interestingly, the majority of tumors were located in the right ovary, with the contralateral ovary remaining unaffected but atrophic. The ovary from heterozygotes also showed pathology after 15 months. None of the age-matched wild-type mice that remained fertile developed any sign of ovarian tumors. Circulating LH and FSH levels were increased in follitropi

  • ovarian pathology and high incidence of sex cord tumors in follitropin receptor knockout forko mice
    Endocrinology, 2001
    Co-Authors: Natalia Danilovich, Indrojit Roy, Ram M Sairam
    Abstract:

    In this investigation we describe our observations of the status of the aging ovary in mice with disruption of the receptor for FSH. Knockout mice at 3–5 months of age are acyclic and sterile, with very small, underdeveloped ovaries. Thus, they exhibit Hypergonadotropic-Hypogonadism with high levels of circulating FSH similar to the postmenopausal state in women. By 12 months more than 92% of these animals developed various kinds of ovarian pathology, including neoplasms of sex cord-stromal type as well as cysts. Interestingly, the majority of tumors were located in the right ovary, with the contralateral ovary remaining unaffected but atrophic. The ovary from heterozygotes also showed pathology after 15 months. None of the age-matched wild-type mice that remained fertile developed any sign of ovarian tumors. Circulating LH and FSH levels were increased in follitropin receptor knockout mice and remained severalfold higher in tumor-bearing animals. The histological appearances of ovarian tumors were simila...

Serdar E Bulun - One of the best experts on this subject based on the ideXlab platform.

  • aromatase and estrogen receptor α deficiency
    Fertility and Sterility, 2014
    Co-Authors: Serdar E Bulun
    Abstract:

    Studies on the phenotypes of women and men with mutations disrupting estrogen biosynthesis and action have significantly advanced our knowledge of the physiologic roles of estrogen in humans. Aromatase deficiency results from autosomal recessive inheritance of mutations in the CYP19A1 gene. It gives rise to ambiguous genitalia in 46,XX fetuses. At puberty, affected girls have Hypergonadotropic Hypogonadism, do not develop secondary sexual characteristics, and exhibit progressive virilization. The affected 46,XY men have normal male sexual differentiation and pubertal maturation. These men, however, are extremely tall and have eunucoid proportions with continued linear growth into adulthood, severely delayed epiphyseal closure, and osteoporosis due to estrogen deficiency. Although estrogen has been shown to be essential for normal sperm production and function in mice, its role in fertility is not clear in men. Thus far, one man and an unrelated woman with estrogen resistance due to mutations in the estrogen receptor α (ESR1) gene have been described. Their clinical presentations are similar to that of aromatase-deficient men and women.

  • aromatase deficiency and estrogen resistance from molecular genetics to clinic
    Seminars in Reproductive Medicine, 2000
    Co-Authors: Serdar E Bulun
    Abstract:

    Our knowledge of the physiologic roles of estrogen in women and men has been advanced by recent descriptions of mutations disrupting estrogen biosynthesis and action. Aromatase deficiency results from autosomal recessive inheritance of mutations in the CYP19 gene. It gives rise to ambiguous genitalia in 46,XX individuals. At puberty, affected girls have Hypergonadotropic Hypogonadism, fail to develop secondary sexual characteristics, and exhibit progressive virilization. The affected 46,XY individuals have normal male sexual differentiation and pubertal maturation. These men are extremely tall and have eunuchoid proportions with continued linear growth into adulthood, lack of epiphyseal closure, and osteoporosis due to estrogen deficiency. Although estrogen was shown to be essential for normal sperm production and function in mice, its role in fertility is not clear in men. Thus far, one estrogen-resistant human, a man with a mutant estrogen receptor-alpha gene, has been described. His clinical presentation was similar to that of aromatase-deficient men.

Manuel Fontoura - One of the best experts on this subject based on the ideXlab platform.

  • 46 xx male disorder of sexual development
    Clinical Pediatric Endocrinology, 2020
    Co-Authors: Mariana Adriao, Sofia Ferreira, Rita Santos Silva, Maria Luisa Garcia, Sofia Doria, Carla Costa, Cintia Castrocorreia, Manuel Fontoura
    Abstract:

    An individual's sexual phenotype is usually determined by the presence or absence of the Y chromosome in the embryo's karyotype, however, due to abnormal X/Y terminal exchange through male meiosis, a few individuals develop male genitalia in the absence of the Y chromosome. This case report presents an adolescent referred to the Pediatric Endocrinology Unit due to bilateral gynecomastia. A diagnosis of Hypergonadotropic Hypogonadism was established and chromosomal analysis disclosed 46,XX karyotype, with the SRY gene locus found on one of his X chromosomes. A multidisciplinary approach, including psychological support and genetic counseling, is ideal for the management of these patients. Neoplastic transformation of the dysgenetic gonads has been described in several cases, and hence self-examinations and regular ultrasounds are commonly advised.

Ikuma Fujiwara - One of the best experts on this subject based on the ideXlab platform.

  • a follow up from infancy to puberty in a japanese male with sry negative 46 xx testicular disorder of sex development carrying a p arg92trp mutation in nr5a1
    Sexual Development, 2019
    Co-Authors: Akiko Saitohakoda, Junko Kanno, Dai Suzuki, Sayaka Kawashima, Miki Kamimura, Koji Hirano, Kiyohide Sakai, Maki Igarashi, Maki Fukami, Ikuma Fujiwara
    Abstract:

    SRY-negative 46,XX testicular disorders of sex development (DSD) are very rare conditions. Recently, we identified a novel heterozygous NR5A1 mutation, p.Arg92Trp (c.274C>T, p.R92W), in 2 unrelated cases of 46,XX testicular/ovotesticular DSD. We report the clinical course from infancy to puberty in a Japanese male with SRY-negative 46,XX testicular DSD, carrying this p.Arg92Trp mutation in NR5A1. The patient naturally acquired the development of a penis and pubic hair during puberty. However, Hypergonadotropic Hypogonadism subsequently developed. More clinical cases will be needed to fully understand the effects of the p.Arg92Trp mutation on the ability to maintain testosterone secretion in 46,XX testicular DSD.

A Kremer P H Themmen - One of the best experts on this subject based on the ideXlab platform.

  • an inactivating mutation of the luteinizing hormone receptor causes amenorrhea in a 46 xx female
    The Journal of Clinical Endocrinology and Metabolism, 1996
    Co-Authors: Sergio P A Toledo, Robert Kraaij, M Post, H G Brunner, Patricia L M Dahia, C Y Hayashida, A Kremer P H Themmen
    Abstract:

    Hypergonadotropic Hypogonadism is characterized by decreased gonadal function due to the inability of the gonads to respond to pituitary gonadotropins. Hypergonadotropic Hypogonadism in females has many causes, among which are ovarian dysgenesis and abnormalities of the ovarian receptors for the pituitary gonadotropins. We evaluated a woman who presented with amenorrhea due to Hypergonadotropic Hypogonadism, but who had structurally normal ovaries. She is a sister of two previously identified 46,XY male pseudohermaphrodites with Leydig cell hypoplasia. Injection of hCG did not cause any change in plasma levels of estradiol or progesterone, suggesting complete ovarian resistance to LH. Analysis of the DNA sequence of the LH receptor gene revealed that the patient is homozygous for the same single base change as her two brothers. This mutation causes substitution of an alanine residue by a proline at position 593. In vitro analysis of the mutant LH receptor in cultured human embryonic kidney 293 cells documented that the receptor is unable to stimulate adenylyl cyclase in response to hCG. Plasma levels of estradiol and progesterone were low, whereas LH and FSH levels were increased. On histological analysis of the ovary, follicles were seen at all developmental stages. Nonetheless, primary amenorrhea had been present for 5 yr, and repeated measurements of plasma estradiol and progesterone indicate that ovulation does not occur. These results document the existence of inherited LH resistance as a cause of primary amenorrhea in women. The combined clinical and molecular observations are consistent with previous experimental data suggesting that in humans, LH is necessary for ovulation but follicular maturation can occur in the presence of FSH alone.