Hypothalamus


The hypothalamus is a small part of the vertebrate brain that contains a number of nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus is located below the thalamus and is part of the limbic system. It forms the basal part of the diencephalon. All vertebrate brains contain a hypothalamus. In humans, it is about the size of an almond.
The hypothalamus has the function of regulating certain metabolic processes and other activities of the autonomic nervous system. It synthesizes and secretes certain neurohormones, called releasing hormones or hypothalamic hormones, and these in turn stimulate or inhibit the secretion of hormones from the pituitary gland. The hypothalamus controls body temperature, hunger, important aspects of parenting and maternal attachment behaviours, thirst, fatigue, sleep, circadian rhythms, and is important in certain social behaviors, such as sexual and aggressive behaviors.

Structure

The hypothalamus is divided into four regions in a parasagittal plane, indicating location anterior-posterior; and three zones in the coronal plane, indicating location medial-lateral. Hypothalamic nuclei are located within these specific regions and zones. It is found in all vertebrate nervous systems. In mammals, magnocellular neurosecretory cells in the paraventricular nucleus and the supraoptic nucleus of the hypothalamus produce neurohypophysial hormones, oxytocin and vasopressin. These hormones are released into the blood in the posterior pituitary. Much smaller parvocellular neurosecretory cells, neurons of the paraventricular nucleus, release corticotropin-releasing hormone and other hormones into the hypophyseal portal system, where these hormones diffuse to the anterior pituitary.

Nuclei

The hypothalamic nuclei include the following:
RegionAreaNucleusFunction
Anterior PreopticPreoptic nucleus
Anterior PreopticVentrolateral preoptic nucleusSleep
Anterior MedialMedial preoptic nucleus
  • Regulates the release of gonadotropic hormones from the adenohypophysis
  • Contains the sexually dimorphic nucleus, which releases GnRH, differential development between sexes is based upon in utero testosterone levels
  • Thermoregulation
    • Anterior MedialSupraoptic nucleus
  • Vasopressin release
  • Oxytocin release
    • Anterior MedialParaventricular nucleus
  • thyrotropin-releasing hormone release
  • corticotropin-releasing hormone release
  • oxytocin release
  • vasopressin release
  • somatostatin round
  • arousal
  • appetite
    • Anterior MedialAnterior hypothalamic nucleus
  • thermoregulation
  • panting
  • sweating
  • thyrotropin inhibition
    • Anterior MedialSuprachiasmatic nucleus
  • Circadian rhythms
    • Anterior LateralLateral nucleusSee – primary source of orexin neurons that project throughout the brain and spinal cord
    Middle MedialDorsomedial hypothalamic nucleus
  • blood pressure
  • heart rate
  • GI stimulation
    • Middle MedialVentromedial nucleus
  • satiety
  • neuroendocrine control
    • Middle MedialArcuate nucleus
  • Growth hormone-releasing hormone
  • feeding
  • Dopamine-mediated prolactin inhibition
    • Middle LateralLateral nucleusSee – primary source of orexin neurons that project throughout the brain and spinal cord
    Middle LateralLateral tuberal nuclei
    Posterior MedialMammillary nuclei
  • memory
    • Posterior MedialPosterior nucleus
  • Increase blood pressure
  • pupillary dilation
  • shivering
  • vasopressin release
    • Posterior LateralLateral nucleusSee – primary source of orexin neurons that project throughout the brain and spinal cord
    Posterior LateralTuberomammillary nucleus
  • arousal
  • feeding and energy balance
  • learning
  • memory
  • sleep

    • Connections

    The hypothalamus is highly interconnected with other parts of the central nervous system, in particular the brainstem and its reticular formation. As part of the limbic system, it has connections to other limbic structures including the amygdala and septum, and is also connected with areas of the autonomous nervous system.
    The hypothalamus receives many inputs from the brainstem, the most notable from the nucleus of the solitary tract, the locus coeruleus, and the ventrolateral medulla.
    Most nerve fibres within the hypothalamus run in two ways.
    Several hypothalamic nuclei are sexually dimorphic; i.e., there are clear differences in both structure and function between males and females. Some differences are apparent even in gross neuroanatomy: most notable is the sexually dimorphic nucleus within the preoptic area, in which the differences are subtle changes in the connectivity and chemical sensitivity of particular sets of neurons. The importance of these changes can be recognized by functional differences between males and females. For instance, males of most species prefer the odor and appearance of females over males, which is instrumental in stimulating male sexual behavior. If the sexually dimorphic nucleus is lesioned, this preference for females by males diminishes. Also, the pattern of secretion of growth hormone is sexually dimorphic; this is why in many species, adult males are visibly distinct sizes from females.

    Responsiveness to ovarian steroids

    Dimorphism is also found in physiological and behavioral responses to ovarian steroids in adults, where males and females respond to these hormones differently. For example, estrogen receptor sensitivity for different sets of neurons is dimorphic already early on in development. Hypothalamic dimorphism underlies some known behavioral differences in mice, and has known physiological effects in humans, e.g. affecting thermoregulation and metabolism. Although human hypothalami exhibit various sex differences, it is not certain which behaviors are caused, predisposed, and not caused by these. In addition to confounding environmental factors, the hypothalamus also contributes to dimorphic human behaviors where the hypothalamus does not itself cause dimorphism, but rather exhibits conditional, dimorphic responses as part of greater pathways, such as the HPG-axis or the HPA-axis.
    Estrogen and progesterone can influence gene expression in particular neurons or induce changes in cell membrane potential and kinase activation, leading to diverse non-genomic cellular functions. Estrogen and progesterone bind to their cognate nuclear hormone receptors, which translocate to the cell nucleus and interact with regions of DNA known as hormone response elements or get tethered to another transcription factor's binding site. Estrogen receptor has been shown to transactivate other transcription factors in this manner, despite the absence of an estrogen response element in the proximal promoter region of the gene. In general, ERs and progesterone receptors are gene activators, with increased mRNA and subsequent protein synthesis following hormone exposure.
    Male and female brains differ in the distribution of estrogen receptors; this is widely assumed to be caused by neonatal estradiol exposure, with some mechanisms being proven, however the complete underlying mechanism remains uncertain. Estrogen and progesterone receptors show differential expression where they are found in neurons of the anterior and mediobasal hypothalamus, notably:
    In neonatal life, gonadal steroids are thought to influence the development of the hypothalamus. For instance, they correlate with the ability of females to exhibit a normal reproductive cycle, and of males and females to display appropriate reproductive behaviors in adult life:
    • If a female rat is given testosterone in the first few days of postnatal life, during the "critical period" of sex-steroid influence in rats, the hypothalamus is irreversibly defeminized and masculinized; the adult rat will be incapable of generating an LH surge in response to estrogen as is characteristic of females, but will be capable of exhibiting male sexual behaviors e.g. mounting a sexually receptive female.
    • By contrast, a male rat castrated just after birth will be feminized, and the adult will show typical female "receptive" sexual behavior in response to estrogen, that is, lordosis behavior.
    • Masculinization and feminization can be distinguished from their complimentary de-feminization and de-masculinization, as neonatal treatment with COX2 inhibitors or PgE2 makes it possible to create rats which exhibit neither sexual behaviour, or both, respectively. Some effects of combined masculinization and feminization on hypothalamic physiology are known, but outcomes where the processes oppose remain unreported in vitro as of 2025.
    In primates, the developmental influence of androgens is less clear, and the consequences are less understood. Within the brain, testosterone is aromatized, which is the principal active hormone for developmental influences. The human testis secretes high levels of testosterone from about week eight of fetal life until five to six months after birth, a process that appears to underlie the male phenotype. Estrogen from the maternal circulation is relatively ineffective, partly because of the high circulating levels of steroid-binding proteins in pregnancy.
    Sex steroids are not the only important influences upon hypothalamic development; in particular, pre-pubertal stress in early life determines the capacity of the adult hypothalamus to respond to an acute stressor. Unlike gonadal steroid receptors, glucocorticoid receptors are very widespread throughout the brain; in the paraventricular nucleus, they mediate negative feedback control of CRF synthesis and secretion, but elsewhere their role is not well understood.