Geoffrey A. Head

Epigenetic Changes Mediate Effects of Hormones on Behavior

Three types of changes in the nerve cell nucleus—DNA methylation, histone protein modification, and synthesis of noncoding RNAs—can play into hormone effects on brain and behavior.

One Hormone Can Have Many Effects

This chapter is designed to study the concept of influence on individual behavior. Some basic experimental examples include hypoglycemia, which initiates counterregulatory hormone release, including growth hormone, cortisol, glycogen, and epinephrine; protein energy malnutrition, where a lack of protein is known to lead to apathy, weakness, hypothermia, and impaired cognitive function; and corticotropin-releasing hormone, which reduces food intake when injected into the brain. Some clinical examples include postmenopausal hormone replacement therapy in which estrogen replacement therapy can ameliorate symptoms such as hot flashes, sweating, insomnia, and headaches; assisted reproduction, in which mature follicles and ovulation are promoted; and endocrine deficiency syndromes, which involve several hormones such as growth hormone and anterior pituitary hormones.

Hormones Can Facilitate or Suppress Behaviors

This chapter highlights the powerful influences of hormones on behavior. Individual hormones can have facilitating or inhibiting effects on behavior, depending on their concentrations and locations in the central nervous system and, especially, on the overall hormonal milieu in which they exert their actions. Most groups of hormones with related metabolic effects are secreted in an orderly fashion, particularly with respect to their time courses. The principle that hormones are capable of either increasing or decreasing certain behaviors can be extended to the molecular mechanisms in forebrain neurons underlying such behavior. In humans, as in laboratory animals, social tendencies include a wide variety of courtship and reproductive behaviors that further the survival of the species: aggressive behaviors, especially for food acquisition and protection of offspring; communicative responses, which convey emotional and behavioral intent; and pure affiliation, providing emotional support and promoting friendly synergy within a group.

There Are Optimal Hormone Concentrations: Too Little or Too Much Can Be Damaging

The majority of endocrine problems are a result of hormones being too much, too little, too early, or too late. The mechanisms of hormone action involve the temporal envelope of its concentration as well as the sensitivity of the cellular response to the hormone. This is mediated by specific receptors that detect and bind to the hormone and then signal to the cell over a variety of pathways, thus shaping the response of the cell. Therefore, determining optimal levels for a given hormone must be achieved by paying attention to these mechanistic steps. The correct timing of the actions of hormones in development is essential for normal growth. The wrong amount of hormone too early can have profound behavioral consequences.

Gene Duplication and Splicing Products for Hormone Receptors in the Central Nervous System Often Have Different Behavioral Effects

Parts of chromosomes may be duplicated as a consequence of the operation of genetic recombination machinery during the passage of chromosomal information from mother and father to offspring. They may end up in tandem positions on the same chromosome, or by the mechanisms of transposition, they may be moved to a different chromosome. It has been argued that such stochasticity represents a major driving force in evolution. This explains why mating behaviors are considered to be at the leading edge of evolutionary change. When one copy of the duplicated gene is subsequently altered, either of two consequences will occur. If the coding region is altered, the properties of the encoded protein may be changed. If the promoter of the gene is altered, the temporal and spatial patterns of expression and/or the physiological regulation of expression may be affected. This chapter focuses on the meaning of this train of events for hormone action.

Hormone Receptors Interact With Other Nuclear Proteins to Influence Hormone Responsiveness

Nuclear hormone receptors comprise some of the best-studied transcriptional systems in eukaryotic molecular biology. Steroids are small lipophilic molecules that cross the blood–brain barrier easily and are widely distributed in the brain. Experiments have been divided into two parts: determining the molecular biology of the nuclear hormone receptors themselves and investigating other nuclear proteins that go under the names coactivators and corepressors. The behavioral mechanisms best worked out are those that control the courtship and mating behaviors of female laboratory animals. A significant number of genes have the following two properties: they are turned on by estrogen administration and their products foster female reproductive behaviors. Nuclear hormone receptors do not sit by themselves on the DNA of neurons and glia, facilitating or repressing transcription. Instead, they participate in assemblies of substantial numbers of proteins that mediate their genomic effects. Such nuclear proteins either foster or block the formation of a complex bridge between the hormone-dependent enhancer sequence and the basal transcriptional machinery.

Hormone Receptors Act by Multiple Interacting Mechanisms

Mechanisms of steroid hormone action have experienced large swings in emphasis and are still being worked out. The discovery that proteins that act as nuclear receptors for steroid, thyroid, and certain other hormones are also transcription factors was intriguing and endocrine investigations could rapidly enter the era of eukaryotic molecular biology. Neurobiologists and others interested in the causation of behavior also realized that some hormone actions in the central nervous system (CNS) are registered too rapidly to depend on nuclear, transcriptional mechanisms. Within the field of molecular endocrinology, interpretations of hormone action as being membrane initiated were often considered antithetical to interpretations relying on transcriptional facilitation. This chapter illustrates rapid actions of hormones in the CNS and shows how rapid, membrane-based effects can actually facilitate later genomic actions. Such data foster a unified view of steroid actions on neurons.

Hormone-Behavior Relations Are Reciprocal

Even as hormones can drive behaviors, in some cases, engaging in a particular behavior can alter hormone levels.

Hormone Combinations Can Be Important for Behavior

Corticotropin-releasing hormone (CRH) causes the release of adrenocorticotropic hormone (ACTH) from the pituitary gland, which, in turn, causes the release of glucocorticoids. CRH has a neuroendocrine effect acting through the median eminence of the ventral hypothalamus. It also potentiates a variety of anxiety-related behaviors and even affects the autonomic nervous system. The effects include increased blood pressure and heart rate, decreased gastric acid secretion, and increased colonic motility. CRH provides the main stimulus for ACTH secretion by the anterior pituitary, but it also influences many behavioral mechanisms in the brain. CRH is synthesized by neurons with cell bodies in the amygdala and axons that project to the locus ceruleus in the pons. The locus ceruleus contains about half the norepinephrine-secreting neurons in the entire central nervous system, and CRH can activate these neurons. CRH acts in other brain areas as well, so it is likely that the anxiogenic effect of CRH administration to experimental animals involves multiple sites of action.

Sex Differences Can Influence Behavioral Responses

Abstract In both animal experimentation and clinical medicine the impacts of sex differences on hormone/behavior relations are very obvious and pervasive. In animals and human beings the most obvious neuroendocrine sex difference is the ability of the female to demonstrate an ovulatory surge of luteinizing hormone whereas the male cannot. In mammalian animals the same schedule of estrogen priming followed by progesterone amplification leads to female-typical courtship behaviors followed by lordosis behavior in the female, but not in the male. Long-term testosterone treatment of laboratory animals leads to intromission and ejaculation in the male but not in the female, even though simple mounting behavior might be exhibited by both sexes. Organizational effects are exerted early in life, during brain development, and affect later responses to stimuli and hormones in adulthood. Activational effects are exerted in adulthood and more directly facilitate or repress specific classes of behaviors in animals and humans. As a result, genetic sex and social gender roles are usually consonant.