The contribution of recombinant DNA techniques to reproductive biology

Stewart, H. J.; Jones, D.; Pascall, John C.; Popkin, R. M.; Flint, A. P. F.

doi:10.1530/jrf.0.0830001

Cited by 14 publications

(2 citation statements)

References 209 publications

(279 reference statements)

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“…25 Our data, together with the fact that thyrotropin secretion is often partially suppressed during the period when chorionic gonadotropin concentrations are maximal, suggest that evolution has led to the selection of physiologic mechanisms that operate close to the border of hyperthyroidism during normal pregnancy. Supported by funds from the European Union Program for Training and Mobility (to Dr. Rodien); by the Belgian Program of University Poles of Attraction, Service for Sciences, Technology and Culture; and by grants from the Fonds de la Recherche Scientifique Médicale and the Fonds National de la Recherche Scientifique.…”

Section: Functional Characterization Of the Mutant Receptormentioning

confidence: 65%

Familial Gestational Hyperthyroidism Caused by a Mutant Thyrotropin Receptor Hypersensitive to Human Chorionic Gonadotropin

et al. 1998

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OME degree of stimulation of the thyroid gland by human chorionic gonadotropin is common during early pregnancy. 1-3 When serum chorionic gonadotropin concentrations are abnormally high -for example, in women with molar pregnancies -overt hyperthyroidism may ensue. The pathophysiologic mechanism is believed to be promiscuous stimulation of the thyrotropin receptor by the excess chorionic gonadotropin. 4,5 The explanation for this stimulation is the close structural relations between chorionic gonadotropin and thyrotropin and between their receptors. 6 Hyperemesis gravidarum is characterized by excessive vomiting in early pregnancy, leading to the loss of 5 percent or more of body weight. 4 It is usually self-limited and therefore of little clinical consequence. 5,7 Some women with the disorder have high serum thyroid hormone concentrations, and a few have sufficient clinical manifestations of hyperthyroidism to warrant short-term treatment with antithyroid drugs. 8,9 Many but not all women with hyperemesis gravidarum and hyperthyroidism have high serum chorionic gonadotropin concentrations, raising the possibility that other factors contribute to the hyperthyroidism. 3,8,9 We describe a woman and her mother who had S recurrent gestational hyperthyroidism and normal serum chorionic gonadotropin concentrations. Both women were heterozygous for a missense mutation in the extracellular domain of the thyrotropin receptor. The mutant receptor was more sensitive than the wild-type receptor to chorionic gonadotropin, thus accounting for the occurrence of hyperthyroidism despite the presence of normal chorionic gonadotropin concentrations. CASE REPORTThe proband was a 27-year-old woman who was 10 weeks' pregnant when referred for the evaluation and treatment of hyperthyroidism. This was her third pregnancy, the first and second having resulted in early miscarriage accompanied by severe nausea and vomiting. She again reported severe nausea and vomiting and had recently lost 5 kg in weight. Physical examination revealed persistent tachycardia (heart rate, 120 beats per minute), excessive sweating, and tremor of the hands. There was a small, diffuse goiter and no ophthalmopathy. Laboratory studies revealed the following values: serum thyrotropin concentration, <0.07 µU per milliliter (normal, 0.2 to 6); serum free thyroxine concentration, 4.7 ng per deciliter (60 pmol per liter; normal, 0.8 to 1.9 ng per deciliter [11 to 24 pmol per liter]); and serum triiodothyronine concentration, 605 ng per deciliter (9.77 nmol per liter; normal, 65 to 170 ng per deciliter [1.05 to 2.75 nmol per liter]). No antibodies to thyroid peroxidase or the thyrotropin receptor were detected in serum.The patient was treated with 450 mg of propylthiouracil per day for eight weeks, and the dose was then tapered to 150 mg per day. Her condition improved rapidly, and she remained clinically and biochemically euthyroid for the rest of her pregnancy. She delivered a normal girl at 38 weeks of gestation, at which time the propylthiouracil was discontinued....

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Section: Functional Characterization Of the Mutant Receptormentioning

confidence: 65%

Familial Gestational Hyperthyroidism Caused by a Mutant Thyrotropin Receptor Hypersensitive to Human Chorionic Gonadotropin

et al. 1998

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“…Recombinant DNA techniques have allowed the cloning and precise determination of the structure of numerous genes. The reader is referred to Alberts et al (1989) for a review of gene structure and function and to a recent review in this journal (Stewart et al, 1988), which covers some of the topics with particular reference to reproductive biology. Many of these techniques are descriptive and allow documentation of the changes in gene expression, but do not give insight into the underlying regulatory mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Genetic manipulation of mammals and its application in reproductive biology

Wilmut

Hooper²,

Simons³

1991

Reproduction

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Methods of genetic manipulation Microinjection Retroviral vectors Embryonal stem cells Spermatozoa as vectors Factors affecting the expression of transgenes Choice of species Assays for transgene expression Research strategies using genetically manipulated animals Ablation of tissues Cell lineages Identification of new genes Modification of gene function Disease models Other uses of oncogenes in transgenic animals Somatic gene therapy Research in reproduction Embryogenesis Homoeobox-containing genes Genomic imprinting Hypogonadal mice and the GnRH gene Development of the reproductive tract Lactation Spermatogenesis Conclusions

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Advances in reproduction in captive, female great apes: Value of biotechniques

Loskutoff

Kraemer

Raphael

et al. 1991

American J Primatol

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Most of the progress in female great ape reproduction has focused on monitoring ovarian and endocrine activity. Perhaps of more importance has been the gradually evolving interest and willingness to consider biotechnology as a potential, viable approach for enhancing reproductive performance. Artificial insemination (AI), in vitro fertilization (IVF), and embryo transfer offer an array of possibilities for combating infertility and understanding the fundamental differences and similarities among great ape species. Multidisciplinary efforts have assessed reproductive competence, from the simple k e . , perineal tumescence and urinary occult blood in chimpanzees) to the complex (i.e., ovum recovery and IVF following exogenous hormone treatment in chimpanzees and gorillas). Hysterosalpingography and laparoscopy have been used to determine uterotubal patency and to identify pathological conditions in gorillas. Assays for steroid metabolites in serial urine samples, to permit accurate assessments of ovarian cyclicity, have been developed and validated for all great apes species. Stimulation of follicular recruitment and maturation has been achieved following administration of clomiphene citrate (chimpanzees and gorillas) and human menopausal gonadotropin (gorillas). Clomiphene citrate and human chorionic gonadotropin have been used to regulate ovulation for the A1 of chimpanzees. Pregnancies have resulted in chimpanzees and gorillas following A1 using fresh and cryopreservedlthawed semen; however, conception rates vary. Embryos have been nonsurgically recovered from chimpanzees after timed matings and follicular oocytes have been recovered from chimpanzees and gorillas by transabdominal laparoscopy after exogenous hormone treatment. To date, although in vivo matured ova have been fertilized in vitro using homologous sperm in chimpanzees and gorillas, no great ape offspring have been born from transferred embryos produced by in vitro or in vivo fertilization. A review of the many remaining problems suggests the need for more basic studies of ovulation induction, ovum and sperm requirements in vivo and in vitro,

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The contribution of recombinant DNA techniques to reproductive biology

Cited by 14 publications

References 209 publications

Familial Gestational Hyperthyroidism Caused by a Mutant Thyrotropin Receptor Hypersensitive to Human Chorionic Gonadotropin

Familial Gestational Hyperthyroidism Caused by a Mutant Thyrotropin Receptor Hypersensitive to Human Chorionic Gonadotropin

Genetic manipulation of mammals and its application in reproductive biology

Advances in reproduction in captive, female great apes: Value of biotechniques

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