Neuroendocrinology of Reproduction

I. Chemical Background of Endocrine Function.- 1. Structure of Protein and Peptide Hormones.- I. Introduction.- II. Peptide Hormones.- A. Posterior Pituitary.- B. Hypothalamus.- C. Anterior Pituitary.- D. Pancreas.- E. Blood.- III. Protein Hormones.- A. Anterior Pituitary and Placenta.- IV. Iodoproteins.- V. Catecholamines and Indoleamines.- References.- 2. Histology of the Pituitary.- I. Introduction.- II. Posterior Pituitary.- III. Anterior Pituitary.- References.- 3. Essentials of Steroid Structure, Nomenclature, Reactions, Biosynthesis, and Measurements.- I. Introduction.- II. Basic Steroid Structure and Nomenclature.- A. Cyclohexane and Stereochemistry.- B. The Steroid Nucleus.- C. Essentials of Steroid Nomenclature.- III. Functional Groups in Steroids and Their Chemical Reactions.- A. Simple Functional Groups.- B. Complex Functional Groups.- C. Steroid Sulfates and Glucuronides.- IV. Enzymes and Steroid Transformations.- A. Hydroxylases.- B. Dehydrogenases.- C. Lyases.- D. Conjugation and Deconjugation Enzymes.- E. Miscellaneous Enzymes.- V. Biosynthesis of Steroids.- A. Biosynthesis of Pregnenolone.- B. Biosynthesis of Progestins.- C. Biosynthesis of Androgens.- D. Biosynthesis of Estrogens.- VI. Selected Methods of Steroid Measurement.- A. Double Isotope Derivatives.- B. Gas-Liquid Chromatography.- C. Saturation Analysis.- VII. Summary.- References.- 4. Neurotransmitter Systems: Anatomy and Pharmacology.- I. Introduction.- II. Methodology of Psychopharmacology.- A. Mode of Action of Neuropharmacological Agents.- B. Psychopharmacological Techniques.- III. Neuroanatomy of Cholinergic and Monoaminergic Pathways.- A. The Norepinephrine Systems.- B. The Epinephrine System.- C. The Dopamine Systems.- D. The Serotonin Systems.- E. The Acetylcholine Systems.- F. The Peptidergic Systems.- References.- II. Development of Reproductive Function.- 5. Hormonal Actions on the Sexual Differentiation of the Genitalia and the Gonadotropin-Regulating Systems.- I. Brief History of the Problem.- II. Normal Embryogenesis of the Genital System.- A. Sex Determination and Differentiation of the Gonads.- B. Differentiation of the Genital Ducts.- C. Differentiation of the Urogenital Sinus and Genital Tubercle.- D. Differentiation of the Mammary Glands.- III. The Effects of Exogenous Estrogens on Embryogenesis of the Genital System.- IV. Disturbances in Embryogenesis of the Genital System.- A. Disturbances of the Sex Determination Process.- B. Disturbances of Gonadal Differentiation.- C. Disturbances of Androgen Action.- D. Disturbances of Mullerian Duct Inhibitor Action.- V. Differentiation of Gonadotropin Release Systems.- A. Age Factors in Differentiation of Gonadotropin Release Patterns.- B. Steroidal Factors in Differentiation of Gonadotropin Release Patterns.- C. Site of Action of Hormones Involved in Differentiation of Gonadotropin Release Patterns.- D. Mechanisms for the Protection of Female Fetuses from Masculinizing Agents.- VI. Summary.- References.- 6. Perinatal Hormones and Their Role in the Development of Sexually Dimorphic Behaviors.- I. Brief History of the Problem.- II. Prenatal Hormones and Their Effects on the Sex Behavior of Adult Guinea Pigs.- III. Eight Questions Regarding "Organizing" Effects of Hormones.- A. Are There "Organizing" and "Activating" Effects of Hormones? A Matter of Terminology.- B. Are There Critical Periods or Periods of Maximal Susceptibility to Perinatal Hormones?.- C. Are There Parallels between Genital Differentiation and Neural Organization?.- D. Organizational Effects-Structural or Functional?.- E. Perinatal Hormones-Are Their Effects on the Nervous System General or Localized?.- F. What Is the Effective Perinatal Hormone-I. Chemical Background of Endocrine Function.- 1. Structure of Protein and Peptide Hormones.- I. Introduction.- II. Peptide Hormones.- A. Posterior Pituitary.- B. Hypothalamus.- C. Anterior Pituitary.- D. Pancreas.- E. Blood.- III. Protein Hormones.- A. Anterior Pituitary and Placenta.- IV. Iodoproteins.- V. Catecholamines and Indoleamines.- References.- 2. Histology of the Pituitary.- I. Introduction.- II. Posterior Pituitary.- III. Anterior Pituitary.- References.- 3. Essentials of Steroid Structure, Nomenclature, Reactions, Biosynthesis, and Measurements.- I. Introduction.- II. Basic Steroid Structure and Nomenclature.- A. Cyclohexane and Stereochemistry.- B. The Steroid Nucleus.- C. Essentials of Steroid Nomenclature.- III. Functional Groups in Steroids and Their Chemical Reactions.- A. Simple Functional Groups.- B. Complex Functional Groups.- C. Steroid Sulfates and Glucuronides.- IV. Enzymes and Steroid Transformations.- A. Hydroxylases.- B. Dehydrogenases.- C. Lyases.- D. Conjugation and Deconjugation Enzymes.- E. Miscellaneous Enzymes.- V. Biosynthesis of Steroids.- A. Biosynthesis of Pregnenolone.- B. Biosynthesis of Progestins.- C. Biosynthesis of Androgens.- D. Biosynthesis of Estrogens.- VI. Selected Methods of Steroid Measurement.- A. Double Isotope Derivatives.- B. Gas-Liquid Chromatography.- C. Saturation Analysis.- VII. Summary.- References.- 4. Neurotransmitter Systems: Anatomy and Pharmacology.- I. Introduction.- II. Methodology of Psychopharmacology.- A. Mode of Action of Neuropharmacological Agents.- B. Psychopharmacological Techniques.- III. Neuroanatomy of Cholinergic and Monoaminergic Pathways.- A. The Norepinephrine Systems.- B. The Epinephrine System.- C. The Dopamine Systems.- D. The Serotonin Systems.- E. The Acetylcholine Systems.- F. The Peptidergic Systems.- References.- II. Development of Reproductive Function.- 5. Hormonal Actions on the Sexual Differentiation of the Genitalia and the Gonadotropin-Regulating Systems.- I. Brief History of the Problem.- II. Normal Embryogenesis of the Genital System.- A. Sex Determination and Differentiation of the Gonads.- B. Differentiation of the Genital Ducts.- C. Differentiation of the Urogenital Sinus and Genital Tubercle.- D. Differentiation of the Mammary Glands.- III. The Effects of Exogenous Estrogens on Embryogenesis of the Genital System.- IV. Disturbances in Embryogenesis of the Genital System.- A. Disturbances of the Sex Determination Process.- B. Disturbances of Gonadal Differentiation.- C. Disturbances of Androgen Action.- D. Disturbances of Mullerian Duct Inhibitor Action.- V. Differentiation of Gonadotropin Release Systems.- A. Age Factors in Differentiation of Gonadotropin Release Patterns.- B. Steroidal Factors in Differentiation of Gonadotropin Release Patterns.- C. Site of Action of Hormones Involved in Differentiation of Gonadotropin Release Patterns.- D. Mechanisms for the Protection of Female Fetuses from Masculinizing Agents.- VI. Summary.- References.- 6. Perinatal Hormones and Their Role in the Development of Sexually Dimorphic Behaviors.- I. Brief History of the Problem.- II. Prenatal Hormones and Their Effects on the Sex Behavior of Adult Guinea Pigs.- III. Eight Questions Regarding "Organizing" Effects of Hormones.- A. Are There "Organizing" and "Activating" Effects of Hormones? A Matter of Terminology.- B. Are There Critical Periods or Periods of Maximal Susceptibility to Perinatal Hormones?.- C. Are There Parallels between Genital Differentiation and Neural Organization?.- D. Organizational Effects-Structural or Functional?.- E. Perinatal Hormones-Are Their Effects on the Nervous System General or Localized?.- F. What Is the Effective Perinatal Hormone-Is It Testosterone or a Metabolite of Testosterone?.- G. Do Perinatal Hormones Influence Noncopulatory as Well as Copulatory Behavior?.- H. Do Prenatal Hormones Influence Behavior of Primates?.- IV. Summary.- References.- 7. Early Organizational Effects of Hormones: An Evolutionary Perspective.- I. Introduction.- A. Definitions and a Note on Taxonomy.- B. Research Questions, Methods, and Strategies.- II. Differentiation of Reproductive Function in Invertebrates..- A. Coelenterates, Nemerteans, and Molluscs.- B. Insects.- C. Crustaceans.- D. Summary.- III. Differentiation of Reproductive Function in Fish (Osteichthyes).- A. Morphology.- B. Behavior.- C. Summary.- IV. Differentiation of Reproductive Function in Amphibians..- A. Gonads.- B. Other Sex Structures.- C. Behavior.- D. Summary.- V. Differentiation of Reproductive Function in Reptiles.- A. Gonads.- B. Other Sex Structures.- C. Behavior.- D. Summary.- VI. Differentiation of Reproductive Function in Birds.- A. Gonads.- B. Other Sex Structures.- C. Ovulation and Oviposition.- D. Behavior.- E. Summary.- VII. Overview.- A. Common Factors in Sex Differentiation (Including Mammalian).- B. Species Differences.- C. Evolution of Sex Differentiation.- D. Areas for Future Research.- E. Conclusions.- References.- 8. Puberty.- I. Introduction.- II. Neuroendocrine Foundations of the Physiology of Puberty.- III. The Problem of Puberty.- A. Ovulatory Hormone Release.- B. The Hypothalamus.- C. Steroid Feedback.- D. Gonadal Maturation.- E. Body Growth.- F. Extrahypothalamic Structures Influencing Puberty.- G. Role of Environmental Cues in Regulating the Onset of Puberty.- H. Pheromonal Influences.- I. Precocious Puberty and Pseudopuberty in Man.- References.- III. Control of Reproduction on the Organismic and Physiological Levels of Organization.- 9. Experimental Analysis of Hormone Actions on the Hypothalamus, Anterior Pituitary, and Ovary.- I. Brief History of the Problem.- II. The Long-Loop System.- A. General Orientation.- B. Steroids Act on the Anterior Hypothalamic-Suprachiasmatic Nucleus and the Preoptic Area.- C. Steroids Act on the Medial Basal Hypothalamus to Influence Pituitary Function.- D. Steroids Act Directly on the Anterior Pituitary.- E. Hypothalamic Hormones Affect Pituitary Hormones...- F. Pituitary Hormones Act on Gonadal Tissue.- III. Pituitary Hormones Affect Pituitary Hormone Secretion-The Short-Loop System.- IV. Releasing Factors Affect Releasing Factor Production-The Ultrashort Loop.- V. Ovarian Hormones Affect the Ovary.- VI. Conclusions.- References.- 10. Estrous Cyclicity in Mammals.- I. Introduction.- II. Rat Estrous Cycles-Ovarian Aspect.- A. Indirect Assessments of Cyclic Release of Ovarian Hormones.- B. Direct Assessments of Cyclic Release of Ovarian Hormones.- III. Rat Estrous Cycles-Pituitary Aspect.- A. Indirect Assessments of Cyclic Release of Pituitary Hormones.- B. Direct Assessments of Cyclic Release of Pituitary Hormones.- IV. Rat Estrous Cycles-Hypothalamic Aspect.- V. The Estrous Cycle-Putting It All Together.- VI. Modeling of the Rat Estrous Cycle.- VII. Hamster Estrous Cycles.- VIII. Guinea Pig Estrous Cycles.- IX. Sheep Estrous Cycles.- A. Basic Patterns of Secretion of Ovarian and Pituitary Hormones.- B. A More Detailed Look at Hormones a Few Days before and at the Periovulatory Period.- C. A More Detailed Look at the Luteal Phase.- D. The Anestrous State.- X. Dog Estrous Cycles.- XI. Rhesus Menstrual Cycles.- XII. Reflex Ovulators-Rabbits.- XIII. Reflex Ovulators-Are Their Effects on the Nervous System General or Localized?.- F. What Is the Effective Perinatal Hormone-Is It Testosterone or a Metabolite of Testosterone?.- G. Do Perinatal Hormones Influence Noncopulatory as Well as Copulatory Behavior?.- H. Do Prenatal Hormones Influence Behavior of Primates?.- IV. Summary.- References.- 7. Early Organizational Effects of Hormones: An Evolutionary Perspective.- I. Introduction.- A. Definitions and a Note on Taxonomy.- B. Research Questions, Methods, and Strategies.- II. Differentiation of Reproductive Function in Invertebrates..- A. Coelenterates, Nemerteans, and Molluscs.- B. Insects.- C. Crustaceans.- D. Summary.- III. Differentiation of Reproductive Function in Fish (Osteichthyes).- A. Morphology.- B. Behavior.- C. Summary.- IV. Differentiation of Reproductive Function in Amphibians..- A. Gonads.- B. Other Sex Structures.- C. Behavior.- D. Summary.- V. Differentiation of Reproductive Function in Reptiles.- A. Gonads.- B. Other Sex Structures.- C. Behavior.- D. Summary.- VI. Differentiation of Reproductive Function in Birds.- A. Gonads.- B. Other Sex Structures.- C. Ovulation and Oviposition.- D. Behavior.- E. Summary.- VII. Overview.- A. Common Factors in Sex Differentiation (Including Mammalian).- B. Species Differences.- C. Evolution of Sex Differentiation.- D. Areas for Future Research.- E. Conclusions.- References.- 8. Puberty.- I. Introduction.- II. Neuroendocrine Foundations of the Physiology of Puberty.- III. The Problem of Puberty.- A. Ovulatory Hormone Release.- B. The Hypothalamus.- C. Steroid Feedback.- D. Gonadal Maturation.- E. Body Growth.- F. Extrahypothalamic Structures Influencing Puberty.- G. Role of Environmental Cues in Regulating the Onset of Puberty.- H. Pheromonal Influences.- I. Precocious Puberty and Pseudopuberty in Man.- References.- III. Control of Reproduction on the Organismic and Physiological Levels of Organization.- 9. Experimental Analysis of Hormone Actions on the Hypothalamus, Anterior Pituitary, and Ovary.- I. Brief History of the Problem.- II. The Long-Loop System.- A. General Orientation.- B. Steroids Act on the Anterior Hypothalamic-Suprachiasmatic Nucleus and the Preoptic Area.- C. Steroids Act on the Medial Basal Hypothalamus to Influence Pituitary Function.- D. Steroids Act Directly on the Anterior Pituitary.- E. Hypothalamic Hormones Affect Pituitary Hormones...- F. Pituitary Hormones Act on Gonadal Tissue.- III. Pituitary Hormones Affect Pituitary Hormone Secretion-The Short-Loop System.- IV. Releasing Factors Affect Releasing Factor Production-The Ultrashort Loop.- V. Ovarian Hormones Affect the Ovary.- VI. Conclusions.- References.- 10. Estrous Cyclicity in Mammals.- I. Introduction.- II. Rat Estrous Cycles-Ovarian Aspect.- A. Indirect Assessments of Cyclic Release of Ovarian Hormones.- B. Direct Assessments of Cyclic Release of Ovarian Hormones.- III. Rat Estrous Cycles-Pituitary Aspect.- A. Indirect Assessments of Cyclic Release of Pituitary Hormones.- B. Direct Assessments of Cyclic Release of Pituitary Hormones.- IV. Rat Estrous Cycles-Hypothalamic Aspect.- V. The Estrous Cycle-Putting It All Together.- VI. Modeling of the Rat Estrous Cycle.- VII. Hamster Estrous Cycles.- VIII. Guinea Pig Estrous Cycles.- IX. Sheep Estrous Cycles.- A. Basic Patterns of Secretion of Ovarian and Pituitary Hormones.- B. A More Detailed Look at Hormones a Few Days before and at the Periovulatory Period.- C. A More Detailed Look at the Luteal Phase.- D. The Anestrous State.- X. Dog Estrous Cycles.- XI. Rhesus Menstrual Cycles.- XII. Reflex Ovulators-Rabbits.- XIII. Reflex Ovulators-Cats.- XIV. Summary.- References.- 11. How the Brain Mediates Ovarian Responses to Environmental Stimuli: Neuroanatomy and Neurophysiology.- I. Introduction.- II. Environmental Influences on Hormone Secretion.- A. Visual and Auditory.- B. Tactile.- C. Olfactory.- III. How Neural Stimuli Produce Hormonal Changes.- A. Role of the Anterior versus Posterior Divisions of the Pituitary Gland.- B. The Hypothalamus as the Final Common Pathway to the Pituitary Gland.- IV. Extrahypothalamic Influences on Hormone Secretion.- A. Olfactory Bulbs.- B. Septum.- C. Amygdala.- D. Hippocampus.- E. Mesencephalic Reticular Formation.- References.- 12 Seasonal Reproduction: Photoperiodism and Biological Clocks.- I. Physiological Mediators.- A. Photoperiod and Seasonality.- B. Photosensitivity and Photorefractoriness.- C. The Pineal Gland and Annual Reproductive Cycles in the Syrian Hamster.- D. The Pituitary-Gonadal Axis and Annual Reproductive Cycles.- E. Annual Rhythms in Other Physiological Functions.- II. Circadian Rhythms and Day Length Measurement.- A. Biological Time Measurement.- B. Models for the Photoperiodic Clock.- C. Entrainment of Circadian Rhythms.- D. Entrainment and Photoperiodic Induction by Skeleton Photoperiods.- E. Entrainment and Photoperiodic Induction when T Is Close to ?.- F. Entrainment and Induction by 24-Hour LD Cycles with Different Photoperiods.- G. Photoperiodic Time Measurement and the Regulation of the Annual Cycle.- III. Summary and Outlook.- References.- IV. Control of Reproduction on the Cellular and Chemical Level.- 13. CNS Control of the Pituitary: Neurochemistry of Hypothalamic Releasing and Inhibitory Hormones.- I. Introduction.- II. Evidence for Hypothalamic Control of Anterior Pituitary.- Hormone Release.- III. The Neurohumoral Hypothesis of Control of Anterior Pituitary Hormone Secretion.- IV. Hypothalamic Releasing and Inhibiting Hormones.- V. Mechanism of Action of Releasing and Inhibiting Hormones on the Pituitary.- VI. Localization of Releasing and Inhibiting Hormones within the Brain.- VII. Factors Affecting Responsiveness of the Adenohypophysis to Releasing and Inhibiting Factors.- VIII. Putative Synaptic Transmitters Involved in Controlling the Release of Releasing Hormones.- IX. The Role of Prostaglandins in Controlling the Release of Releasing Factors and in Stimulating the Release of Pituitary Hormones by Direct Action on the Pituitary Gland.- X. Extrapituitary Actions of Releasing Factors.- XI. Summary.- References.- 14. The Neurochemical Control of Mating Behavior.- I. Introduction.- II. Neuropharmacology of Female Sexual Behavior.- A. Introduction.- B. Monoamines and Female Sexual Behavior.- C. Serotonin and Female Sexual Behavior.- D. Dopamine and Female Sexual Behavior.- E. Norepinephrine and Female Sexual Behavior.- F. Acetylcholine and Female Sexual Behavior.- G. Monamines and Lordosis in Male Rats.- H. Peptides and Lordosis.- I. Monoamines and Sexual Motivation.- J. Monoamines and Maternal Behavior.- K. Summary.- III. Neuropharmacology of Male Sexual Behavior.- A. Introduction.- B. Monoamines and Male Sexual Behavior.- C. Serotonin and Male Sexual Behavior.- D. Dopamine and Male Sexual Behavior.- E. Norepinephrine and Male Sexual Behavior.- F. Acetylcholine and Male Sexual Behavior.- G. Peptides and Male Sexual Behavior.- H. Monoamines and Mounting in Female Rats.- I. Monoamines and Sexual Behavior in Humans.- J. Summary.- IV. Effects of Gonadal Hormones on Central Neurotransmitters.- A. Effects of Estrogen and Progesterone.- B. Effects of Testosterone.- C. Possible Mechanisms of Hormone-Induced Alterations in Neurotransmitter Function.- V. Summary and Review.- References.- 15. Cellular Biochemistry of Hormone Action in Brain and Pituitary.- I. Introduction.- II. Cellular Mechanisms of Hormone Action.- III. Methods for Measuring Receptors.- A. Cell Surface Receptors for Releasing Hormones in Pituitary as Revealed by Biochemical Analysis.- B. Steroid Hormone Receptors in Brain and Pituitary.- C. Thyroid Hormone Receptors in Pituitary and Brain.- IV. Functional Aspects of Hormone-Receptor Interactions in Mature Neuroendocrine Tissues.- A. Releasing Hormones.- B. Thyroid Hormone.- C. Steroid Hormones: Topography of Receptors.- D. Steroid Hormones: Functioning of Receptors.- V. Development Actions of Hormones.- A. Thyroid Hormone.- B. Gonadal Steroids.- VI. Conclusion.- References.- 16. Autoradiographic Technique for Steroid Hormone Localization: Application to the Vertebrate Brain.- I. Introduction.- II. Procedures for Production of Steroid Hormone Autoradiograms.- A. Preparation of Emulsion-Coated Slides.- B. Isotope Administration, Brain Removal, and Freezing..- C. Sectioning and Mounting Autoradiograms in the Darkroom.- D. Exposure, Developing, and Staining Procedures.- E. Controls for Autoradiographic Artifact.- III. Analysis of Autoradiograms.- IV. Experimental Findings after Steroid Autoradiography by the Technique Described.- A. Concentration of Estradiol and Testosterone by Neurons Is a Common Phenomenon among Vertebrates.- B. Striking Similarities across Species in the Neuroanatomical Distribution of Sex-Hormone-Concentrating Cells.- C. Estradiol- and Testosterone-Concentrating Neurons Are Found in Brain Regions That Have Been Implicated in the Control of Hormone-Dependent Functions.- References.- 17. Electrophysiological Effects of Steroid Hormones in Brain Tissue.- I. Introduction.- II. Estradiol.- III. Testosterone.- IV. Corticosterone.- V. Progesterone.- VI. Outlook.- References.- Appendix: A Gross Anatomical Study of the Peripheral Nerves Associated with Reproductive Function in the Female Albino Rat.- I. Introduction.- II. Methods.- III. Results.- A. Femoral Nerve.- B. Genitofemoral Nerve.- C. Pelvic and Hypogastric Nerves.- D. Pudendal and Caudal Cutaneous Femoral Nerves.- References.