Structure and Function of the Gonadotropins

In September of 1977 scientists from many countries met at the Asticou Inn in Maine to present and discuss papers written especially for this monograph. The presentations were informal and directed to the special interests of the audience in order to generate discussions. The authors, many of whom are pioneers and leaders in their field, then had the oppor­ tunity to revise their contributions, which were brought together with the edited discussions to form this volume. The basic research studies presented here are important because of the essential role of gonadotropins in regulating the ovary and testis. This monograph will therefore be of interest to those concerned with fertility regulation, population control, possible new methods for contraception, and to those concerned with reproduction in domestic animals. Re­ searchers in other fields may find this monograph useful, as it has been de­ termined that gonadotropins are secreted by many tumors and are im­ plicated in many cancers. Human choriogonadotropin also seems to be found in most, if not all, cells of the human body. The significance of this, however, is unknown.

1 Mechanism of Action of Gonadoptropins and the Regulation of Gene Expression.- 1. Introduction.- 2. Development of the cAMP–Protein Kinase System in the Neonatal Rat Ovary.- 3. Cyclic-AMP-Dependent Ovarian Nuclear Protein Kinase.- 4. Nuclear Translocation of Ovarian Cytoplasmic cAMP-Dependent Protein Kinase―Mechanism of Translocation.- 5. Functional Importance of Protein Kinase Translocation.- 6. Correlation between Gonadotropin Action and Ovarian Nuclear Activity.- 7. Conclusion.- Discussion.- References.- 2 Chemical Approaches to the Structure-Function Relationships of Luteinizing Hormone (Lutropin).- 3 Structural and lmmunochemical Properties of Human Choriogonadotropin.- 1. Introduction.- 2. Purification.- 3. Structure.- 4. Carbohydrate Function.- 5. Synthesis.- 6. Immunochemistry and Immunoassay.- 7. Biological Activities Present in “Crude” and “Purified” hCG.- Discussion.- References.- 4.Glycoprotein Hormones: Some Aspects of Studies of Secondary and Tertiary Structure.- 1. Introduction.- 2. Disulfide Bonds.- 3. Circular Dichroism Spectra.- Discussion.- References.- 5 Autoradiographic Localization of FSH-Binding Sites on Sertoli Cells and Spermatogonia in Testes from Hypophysectomized Rats.- 1. Introduction.- 2. Experimental Methods.- 3. Results.- 4. Comments.- Discussion.- References.- 6 Serum-Factor- and Prolactin-Induced Stimulation of DNA Synthesis by Nuclei Externalized from Mammary Tissue.- 1 Introduction.- 2. Methods.- 3. Results.- 4. Discussion.- Discussion.- References.- 7 Target Cell Prolactin.- 1. Rationale.- 2. Materials and Methods.- 3. Endogenous Prolactin in Milk and inside Active Milk-Secretory Cells of the Midlactational, Pup-Deprived Rat.- 4. Endogenous Prolactin in Ovaries and in Adrenal and Mammary Glands of the Midlactational, Non-Pup-Deprived Rat.- 5. Studies of Mammary Glands and Corpora Lutea of Estrogen-Treated Postpartum Rats.- 6. Endogenous Prolactin in Prolactin Target Tissues of the Male Rat.- 7. Binding Sites for Homologous Exogenous Prolactin in Male and Female Prolactin Target Tissues―Comparisons with the Presence of Endogenous Prolactin in These Tissues.- 8. Conclusion.- Discussion.- References.- 8 The Structure and Function of Follicle-Stimulating Hormone.- 1. Introduction.- 2. Human Pituitary FSH.- 3. Equine Pituitary FSH.- 4. Ovine Pituitary FSH.- 5. Pituitary FSH from Other Sources.- 6. Urinary FSH.- 7. Function of FSH.- Discussion.- References.- 9 The Biosynthesis of Prolactin.- 1. Introduction.- 2. Cell-Free Translation of Prolactin Messenger RNA.- 3. Regulation of Prolactin Synthesis.- 4. Estrogenic Regulation of Preprolactin Messenger RNA Levels.- 5. Summary.- Discussion.- References.- 10 The Biosynthesis of Chorionic Gonadotropin and Placental Lactogen in First- and Third-Trimester Human Placenta.- 1. Introduction.- 2. Methods.- 3. Results.- 4. Discussion.- 5. Future Projections.- Discussion.- References.- 11 The Interaction of Follitropin (FSH) with Membrane-Bound and Solubilized Gonadal Receptors and Adenylate Cyclase.- 1. Interaction of Follitropin with Receptors in Rat Testis.- 2. Interaction of Follitropin with Ovarian Receptors.- 3. Interaction of Follitropin with Receptors in Bovine Testis.- 4. Solubilization of the Follitropin Receptor.- 5. Some Characteristics of the Solubilized Receptor and Properties of Its Interaction with Follitropin.- 6. Interaction of Follitropin with Testicular Adenylate Cyclase.- 7. Factors That Affect Interaction (in Vitro) of Follitropin with Receptor and Stimulation of Adenylate Cyclase.- 8. Inhibitors of Follitropin Binding to Gonadal Receptors.- References.- 12 Drug Effects on Lutropin Action.- 1. Introduction.- 2. Inhibition of Lutropin Action by Antimalarial Drugs.- 3. Prostaglandins and Lutropin Action.- 4. Effect of 1-Methyl-3-isobutyl Xanthine on Lutropin Action 288.- 5. Concluding Remarks.- Discussion.- References.- 13 Effects of FSH and LH on RNA Synthesis in the Testis: Role of Ornithine Decarboxylase.- 14 Regulation of Gene Expression in the Nucleus by Gonadotropins.- 15 Glycoprotein Hormones and Their Subunits― Immunological and Biological Characterization.- 1. Introduction.- 2. Immunological Behavior.- 3. Forms of Glycoprotein Hormones in Tissues and Fluids.- 4. Abnormal Human Chorionic Gonadotropin Production.- 5. Ubiquity of Human Chorionic Gonadotropin.- Discussion.- References.- 16 Biochemical and Biological Properties of Fish Gonadotropins and Their Subunits: Comparison with Mammalian Hormones.- 1. Introduction.- 2. Purification and Biological Properties of Fish Gonadotropins.- 3. Biochemistry of Fish Gonadotropins and Their Subunits.- 4. Conclusions.- References.- 17 Molecular Aspects of the Subunit Assembly of Glycoprotein Hormones.- 1. Introduction.- 2. Three-Dimensional Features of the Active Conformation of Glycoprotein Hormones.- 3. Assessment of the Conformational Changes Induced by the Assembly of the Subunits.- 4. Kinetic Mechanism of Subunit Assembly.- 5. Subunit Assembly: A Biological Mechanism for Controlling the Active State of the Hormone?.- References.- 18 Biological and Immunological Distinctions between Pituitary and Serum LH in the Rat.- 1. Introduction.- 2. Methods.- 3. Findings and Interpretations.- 4. Discussion.- Discussion.- References.- 19 Parallels in the Modes of Action of Peptide and Steroid Hormones: Membrane Effects and Cellular Entry.- 1. Introduction and Conceptual Framework.- 2. Cellular Entry of Peptide Hormones.- 3. Membrane Recycling and Vesicular Flow.- 4. Lysosomal Compartmentation of Receptor.- 5. Receptor Transport to the Plasmalemma: Postulated Correlation with Lysosome Activation.- 6. Autoregulation of Receptor Biosynthesis and Translocation.- 7. Nuclear Accumulation―Common to Hormone Classes.- 8. Prospectus and Concluding Remarks.- Discussion.- References.- 20 Timing and Sites of Testicular Effects of FSH in Vivo.- 1. Introduction.- 2. Effects of FSH in the Immature Testis.- 3. Adult Testis.- 4. Summary and Conclusions.- Discussion.- References.- 21 Leydig-Cell Responsiveness to LH-Hcg Stimulation: Mechanisms of hCG- and Steroid-Induced Refractoriness.- 1. Introduction.- 2. In Vivo Desensitization to Human Chorionic Gonadotropin.- 3. Variations in the Number of Receptors for Human Chorionic Gonadotropin during Desensitization and Recovery: Down-Regulation.- 4. Mechanism of Down-Regulation.- 5. Leydig-Cell Responsiveness to Human Chorionic Gonadotropin and Dibutyryl Cyclic AMP in Vitro during the Desensitization Period.- 6. Desensitization in Hypophysectomized Animals.- 7. Corticoid-Induced Refractoriness.- 8. Estrogen-Induced Refractoriness.- 9. Discussion.- References.- 22 FSH and the Sertoli Cell.- 1. Introduction.- 2. FSH Binding in the Testis.- 3. Stimulation of Cyclic AMP by FSH.- 4. Androgens and the Function of the Sertoli Cell.- 5. Androgen-Binding Protein; A Sertoli-Cell Product under Hormonal Control.- 6. Role of the Sertoli Cell in FSH Feedback Regulation.- 7. Concluding Comments.- References.- 23 Immunocytochemical Demonstration of Endogenous Membrane and Intracellular Gonadotropin-Binding Sites in the Fetal Rat Testis.- 1. Introduction.- 2. Materials and Methods.- 3. Results.- 4. Dis­cussion.- 5. Summary and Conclusions.- References.- 24 Gonadotropin-Target Cell Interactions: A Model Based on Morphological Localization.- 1. Introduction.- 2. Materials and Methods.- 3. Results.- 4. Discussion.- References.- 25 Localization of Human Chorionic Gonadotropin in Lysosomes of Ovine Luteal Cells.- 1. Introduction.- 2. Materials and Methods.- 3. Results and Discussion.- 4. Conclusions.- Discussion of Chapters 23–25.- References.