Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-27T23:51:43.553Z Has data issue: false hasContentIssue false

25 - Pharmacodynamics and Pharmacokinetics of Gonadotrophins

from PART II - INFERTILITY EVALUATION AND TREATMENT

Published online by Cambridge University Press:  04 August 2010

By
A. Michele Schuler  and
Jonathan G. Scammell
Edited by
Botros R. M. B. Rizk ,
Juan A. Garcia-Velasco ,
Hassan N. Sallam  and
Antonis Makrigiannakis
Botros R. M. B. Rizk
Affiliation:
University of South Alabama
Juan A. Garcia-Velasco
Affiliation:
Rey Juan Carlos University School of Medicine,
Hassan N. Sallam
Affiliation:
University of Alexandria School of Medicine
Antonis Makrigiannakis
Affiliation:
University of Crete
Get access

Summary

INTRODUCTION

Exogenous hormone supplementation has been used to treat infertility for nearly 100 years (1). Compounds extracted from urine and serum have been used in pharmacotherapeutic preparations as the mainstay of exogenous hormone supplementation until recently. These preparations enabled clinicians to manipulate the hypothalamic-pituitary-ovarian axis to induce follicular recruitment and subsequent ovulation in otherwise anovulatory infertile patients. A resurgence of interest in the treatment of infertility occurred with the birth of the first infant following successful in vitro fertilization (IVF), baby Louise Brown. It is interesting that this pregnancy did not result from exogenous hormone supplementation but rather from a noninduced ovulation (2). Nevertheless, with this successful pregnancy came renewed interest in treatment of infertility. This interest has resulted in the development of new technologies for the production of better, safer, and more affordable treatment options for the infertile female patient.

Ovulation of a single healthy oocyte in a natural cycle is a carefully orchestrated event modulated by secretion of several glycoproteins that act on the ovary and other reproductive tissues to stimulate changes in functional morphology and to stimulate steroidogenesis (Table 25.1). Follicle-stimulating hormone (FSH) is secreted from the anterior pituitary gland in response to the secretion of gonadotropin-releasing hormone from the hypothalamus. Circulating FSH stimulates follicular growth in the ovary by acting on specific FSH receptors in the cell membranes of granulosa cells.

Keywords

animal modelschorionic gonadotropincontrolled ovarian stimulationfollicle-stimulating hormonepharmacokineticspharmacodynamicsluteinizing hormone
Type
Chapter
Information
Infertility and Assisted Reproduction , pp. 228 - 234
Publisher: Cambridge University Press
Print publication year: 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Ludwig, M, Diedrich, K. Follow-up of children born after assisted reproductive technologies. Reprod Biomed Online 2002; 5: 317–22.CrossRefGoogle ScholarPubMed
Steptoe, PC, Edwards, RG. Birth after the reimplantation of a human embryo. Lancet 1978; 2: 366.CrossRefGoogle ScholarPubMed
Stouffer, RL, Zelinski-Wooten, MB. Overriding follicle selection in controlled ovarian stimulation protocols: quality vs quantity. Reprod Biol Endocrinol 2004; 2: 32.CrossRefGoogle ScholarPubMed
Srisuparp, S, Strakova, Z, Fazleabas, AT. The role of chorionic gonadotropin (CG) in blastocyst implantation. Arch Med Res 2001; 32: 627–34.CrossRefGoogle Scholar
Ludwig, M, Doody, KJ, Doody, KM. Use of recombinant human chorionic gonadotropin in ovulation induction. Fertil Steril 2003; 79: 1051–9.CrossRefGoogle ScholarPubMed
[No authors listed]. Recombinant follicle stimulating hormone: development of the first biotechnology product for the treatment of infertility. Recombinant Human FSH Product Development Group. Hum Reprod Update 1998; 4: 862–81.
Wheatley, M, Hawtin, SR. Glycosylation of G-protein-coupled receptors for hormones central to normal reproductive functioning: its occurrence and role. Hum Reprod Update 1999; 5: 356–64.CrossRefGoogle ScholarPubMed
Fan, QR, Hendrickson, WA. Structure of human follicle- stimulating hormone in complex with its receptor. Nature 2005; 433: 269–77.CrossRefGoogle ScholarPubMed
Gudermann, T, Brockmann, H, Simoni, M, Gromoll, J, Nieschlag, E. In vitro bioassay for human serum follicle-stimulation hormone (FSH) based on L cells transfected with recombinant rat FSH receptor: validation of a model system. Endocrinology 1994; 135: 2204–13.CrossRefGoogle Scholar
Gromoll, J, Simoni, M. Genetic complexity of FSH receptor function. Trends Endocrinol Metab 2005; 16: 368–73.CrossRefGoogle ScholarPubMed
Bavister, BD, Dees, C, Schultz, RD. Refractoriness of rhesus monkeys to repeated ovarian stimulation by exogenous gonadotropins is caused by nonprecipitating antibodies. Am J Reprod Immunol Microbiol 1986; 11: 11–16.CrossRefGoogle ScholarPubMed
Schuler, AM, Westberry, JM, Scammell, JG, Abee, CR, Kuehl, TJ, Gordon, JW. Ovarian stimulation of squirrel monkeys (Saimiri boliviensis boliviensis) using pregnant mare serum gonadotropin. Comp Med 2005; 56: 12–6.Google Scholar
Cotonnec, JY, Porchet, HC, Beltrami, V, Munafo, A. Clinical pharmacology of recombinant human luteinizing hormone: Part I. Pharmacokinetics after intravenous administration to healthy female volunteers and comparison with urinary human luteinizing hormone. Fertil Steril 1998; 69: 189–94.CrossRefGoogle ScholarPubMed
Cotonnec, JY, Porchet, HC, Beltrami, V, Munafo, A. Clinical pharmacology of recombinant human luteinizing hormone: Part II. Bioavailability of recombinant human luteinizing hormone assessed with an immunoassay and an in vitro bioassay. Fertil Steril 1998; 69: 195–200.CrossRefGoogle ScholarPubMed
Dufau, ML. The luteinizing hormone receptor. Annu Rev Physiol 1998; 60: 461–96.CrossRefGoogle ScholarPubMed
Segaloff, DL, Ascoli, M. The lutropin/chorionic gonadotropin receptor…4 years later. Endocr Rev 1993; 14: 324–47.Google Scholar
Filicori, M, Cognigni, GE, Pocognoli, P, Ciampaglia, W, Bernardi, S. Current concepts and novel applications of LH activity in ovarian stimulation. Trends Endocrinol Metab 2003; 14: 267–73.CrossRefGoogle ScholarPubMed
Menon, KM, Munshi, UM, Clouser, CL, Nair, AK. Regulation of luteinizing hormone/human chorionic gonadotropin receptor expression: a perspective. Biol Reprod 2004; 70: 861–6.CrossRefGoogle ScholarPubMed
Huirne, JA, Lambalk, CB, Loenen, AC, Schats, R, Hompes, PG, Fauser, BC, Macklon, NS. Contemporary pharmacological manipulation in assisted reproduction. Drugs 2004; 64: 297–322.CrossRefGoogle ScholarPubMed
Stenman, UH, Tiitinen, A, Alfthan, H, Valmu, L. The classification, functions and clinical use of different isoforms of hCG. Hum Reprod Update 2006; 12: 769–84.CrossRefGoogle ScholarPubMed
Fares, F. The role of O-linked and N-linked oligosaccharides on the structure-function of glycoprotein hormones: development of agonists and antagonists. Biochim Biophys Acta 2006; 1760: 560–7.CrossRefGoogle ScholarPubMed
Trinchard-Lugan, I, Khan, A, Porchet, HC, Munafo, A. Pharmacokinetics and pharmacodynamics of recombinant human chorionic gonadotrophin in healthy male and female volunteers. Reprod Biomed Online 2002; 4: 106–15.CrossRefGoogle ScholarPubMed
Griesinger, G, Diedrich, K, Devroey, P, Kolibianakis, EM. GnRH agonist for triggering final oocyte maturation in the GnRH antagonist ovarian hyperstimulation protocol: a systematic review and meta-analysis. Hum Reprod Update 2006; 12: 159–68.CrossRefGoogle ScholarPubMed
Schrago, CG. On the time scale of New World primate diversification. Am J Phys Anthropol 2007; 132: 344–54.CrossRefGoogle ScholarPubMed
Zhang, FP, Rannikko, AS, Manna, PR, Fraser, HM, Huhtaniemi, IT. Cloning and functional expression of the luteinizing hormone receptor complementary deoxyribonucleic acid from the marmoset monkey testis: absence of sequences encoding exon 10 in other species. Endocrinology 1997; 138: 2481–90.CrossRefGoogle ScholarPubMed
Gromoll, J, Wistuba, J, Terwort, N, Godmann, M, Muller, T, Simoni, M. A new subclass of the luteinizing hormone/chorionic gonadotropin receptor lacking exon 10 messenger RNA in the New World monkey (Platyrrhini) lineage. Biol Reprod 2003; 69: 75–80.CrossRefGoogle ScholarPubMed
Gromoll, J, Lahrmann, L, Godmann, M, Muller, T, Michel, C, Stamm, S, Simoni, M. Genomic checkpoints for exon 10 usage in the luteinizing hormone receptor type 1 and type 2. Mol Endocrinol 2007; 21: 1984–96.CrossRefGoogle ScholarPubMed
Gromoll, J, Eiholzer, U, Neischlag, E, Simoni, M. Male hypogonadism caused by homozygous deletion of exon 10 of the luteinizing hormone (LH) receptor: differential action of human chorionic gonadotropin and LH. J Clin Endocrinol Metab 2000; 85: 2281–6.CrossRefGoogle ScholarPubMed
Zhang, FP, Kero, J, Huhtaniemi, I. The unique exon 10 of the human luteinizing hormone receptor is necessary for expression of the receptor protein at the plasma membrane in the human luteinizing hormone receptor, but deleterious when inserted into the human follicle-stimulating hormone receptor. Mol Cell Endocrinol 1998; 142: 165–74.CrossRefGoogle ScholarPubMed
Muller, T, Gromoll, J, Simoni, M. Absence of exon 10 of the human luteinizing hormone (LH) receptor impairs LH, but not human chorionic gonadotropin action. J Clin Endocrinol Metab 2003; 88: 2242–9.CrossRefGoogle Scholar
Muller, T, Simoni, M, Pekel, E, Luetjens, CM, Chandolia, R, Amato, F, Norman, RJ, Gromoll, J. Chorionic gonadotrophin beta subunit mRNA but not luteinising hormone beta subunit mRNA is expressed in the pituitary of the common marmoset (Callitrix jacchus). J Mol Endocrinol 2004; 32: 115–28.CrossRefGoogle Scholar
Scammell, JG, Funkhouser, JD, Moyer, FS, Gibson, SV, Willis, DL. Molecular cloning of pituitary glycoprotein α-subunit and follicle stimulating hormone and chorionic gonadotropin β-subunits from New World squirrel monkey and owl monkey. Gen Comp Endocrinol 2008; 155 (3): 534–41.CrossRefGoogle ScholarPubMed
Matzuk, MM, Hsueh, AJ, Lapolt, P, Tsafriri, A, Keen, JL, Boime, I. The biological role of the carboxyl-terminal extension of human chorionic gonadotropin [corrected] beta-subunit. Endocrinology 1990; 126; 376–83.CrossRefGoogle ScholarPubMed
Saal, W, Glowania, HJ, Hengst, W, Happ, J. Pharmacodynamics and pharmacokinetics after subcutaneous and intramuscular injection of human chorionic gonadotropin. Fertil Steril 1991; 56: 225–9.CrossRefGoogle ScholarPubMed
Amato, F, Simula, AP, Gameau, LJ, Norman, RJ. Expression, characterization and immunoassay of recombinant marmoset chorionic gonadotrophin dimer and beta-subunit. J Endocrinol 1998; 159: 141–51.CrossRefGoogle Scholar
Simula, AP, Amato, F, Faast, R, Lopata, A, Berka, J, Norman, RJ. Luteinizing hormone/chorionic gonadotropin bioactivity in the common marmoset (Callithrix jacchus) is due to a chorionic gonadotropin molecule with a structure intermediate between human chorionic gonadotropin and human luteinizing hormone. Biol Reprod 1995; 53: 380–9.CrossRefGoogle ScholarPubMed
Maston, GA, Ruvolo, M. Chorionic gonadotropin has a recent origin within primates and an evolutionary history of selection. Mol Biol Evol 2002; 19: 320–35.CrossRefGoogle Scholar
Kumar, TR. What have we learned about gonadotropin function from gonadotropin subunit and receptor knockout mice?Reproduction 2005; 130: 293–302.CrossRefGoogle ScholarPubMed
Kumar, TR, Wang, Y, Lu, N, Matzuk, MM. Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nat Genet 1997; 15: 201–4.CrossRefGoogle Scholar
Abel, MH, Wootton, AN, Wilkins, V, Huhtaniemi, I, Knight, PG, Charlton, HM. The effect of a null mutation in the follicle-stimulating hormone receptor gene on mouse reproduction. Endocrinology 2000; 141: 1795–803.CrossRefGoogle ScholarPubMed
Ma, X, Dong, Y, Matzuk, MM, Kumar, TR. Targeted disruption of luteinizing hormone beta-subunit leads to hypogonadism, defects in gonadal steroidogenesis, and fertility. Proc Natl Acad Sci USA 2004; 101: 17294–9.CrossRefGoogle Scholar
Zhang, FP, Poutanen, M, Wilbertz, J, Huhtaniemi, I. Normal prenatal but arrested postnatal sexual development in luteinizing hormone receptor knockout (LuRKO) mice. Mol Endocrinol 2001; 15: 172–83.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×