User:Cs4652/Neuroendocrinology

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The endocrine system consists of numerous glands throughout the body that produce and secrete hormones of diverse chemical structure, including peptides, steroids, and neuroamines. Collectively, hormones regulate many physiological processes.

Neuroendocrine system

Major Regulatory Organs

• Hypothalamus
• Pituitary Gland (Anterior and Posterior Pituitary)

Hypothalamus

Hypothalamic interaction with the posterior and anterior pituitary glands. The hypothalamus produces the hormones oxytocin and vasopressin in its endocrine cells (left). These are released at nerve endings in the posterior pituitary gland and then secreted into the systemic circulation. The hypothalamus releases tropic hormones into the hypophyseal portal system to the anterior pituitary (right). The anterior pituitary then secretes trophic hormones into the circulation which elicit different responses from various target tissues. These responses then signal back to the hypothalamus and anterior pituitary to either stop producing or continue to produce their precursor signals.

Main article: Hypothalamus

The Hypothalamus is commonly known as the relay center of the brain because of its role in integrating inputs from all areas of the brain and producing a specific response. In the neuroendocrine system, the hypothalamus receives electrical signals from different parts of the brain and translates those electrical signals into chemical signals in the form of hormones or releasing factors. These chemicals are then transported to the pituitary gland and from there to the systemic circulation.

Pituitary gland

The pituitary gland is divided into two sections: the anterior pituitary and the posterior pituitary. The hypothalamus controls the anterior pituitary's hormone secretion by sending releasing factors, called tropic hormones, down the hypothalamohypophysial portal system. For example, thyrotropin-releasing hormone released by the hypothalamus in to the portal system stimulates the secretion of thyroid-stimulating hormone by the anterior pituitary.

The posterior pituitary is directly innervated by the hypothalamus; the hormones oxytocin and vasopressin are synthesized by neuroendocrine cells in the hypothalamus and stored at the nerves' ends in the posterior pituitary. They are secreted directly into systemic circulation by the hypothalamic neurons.

Major neuroendocrine axes

• Hypothalamic–pituitary–adrenal axis (HPA axis)
• Hypothalamic–pituitary–thyroid axis (HPT axis)
• Hypothalamic–pituitary–gonadal axis (HPG axis)
• Hypothalamic–neurohypophyseal system

Oxytocin and vasopressin (also called anti-diuretic hormone), the two neurohypophysial hormones of the posterior pituitary gland (the neurohypophysis), are secreted from the nerve endings of magnocellular neurosecretory cells into the systemic circulation. The cell bodies of the oxytocin and vasopressin neurons are in the paraventricular nucleus and supraoptic nucleus of the hypothalamus, respectively, and the electrical activity of these neurons is regulated by afferent synaptic inputs from other brain regions.

By contrast, the hormones of the anterior pituitary gland (the adenohypophysis) are secreted from endocrine cells that, in mammals, are not directly innervated, yet the secretion of these hormones (adrenocorticotrophic hormone, luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, prolactin, and growth hormone) remains under the control of the hypothalamus. The hypothalamus controls the anterior pituitary gland via releasing factors and release-inhibiting factors; these are substances released by hypothalamic neurons into blood vessels at the base of the brain, at the median eminence. These vessels, the hypothalamo-hypophysial portal vessels, carry the hypothalamic factors to the anterior pituitary, where they bind to specific receptors on the surface of the hormone-producing cells.

For example, the secretion of growth hormone is controlled by two neuroendocrine systems: the growth hormone-releasing hormone (GHRH) neurons and the somatostatin neurons, which stimulate and inhibit GH secretion, respectively. The GHRH neurones are located in the arcuate nucleus of the hypothalamus, whereas the somatostatin cells involved in growth hormone regulation are in the periventricular nucleus. These two neuronal systems project axons to the median eminence, where they release their peptides into portal blood vessels for transport to the anterior pituitary. Growth hormone is secreted in pulses, which arise from alternating episodes of GHRH release and somatostatin release, which may reflect neuronal interactions between the GHRH and somatostatin cells, and negative feedback from growth hormone.

Functions

The neuroendocrine systems control reproduction in all its aspects, from bonding to sexual behaviour. They control spermatogenesis and the ovarian cycle, parturition, lactation, and maternal behaviour. They control the body's response to stress and infection. They regulate the body's metabolism, influencing eating and drinking behaviour, and influence how energy intake is utilised, that is, how fat is metabolised. They influence and regulate mood, body fluid and electrolyte homeostasis, and blood pressure.

The neurons of the neuroendocrine system are large; they are mini factories for producing secretory products; their nerve terminals are large and organised in coherent terminal fields; their output can often be measured easily in the blood; and what these neurons do and what stimuli they respond to are readily open to hypothesis and experiment. Hence, neuroendocrine neurons are good "model systems" for studying general questions, like "how does a neuron regulate the synthesis, packaging, and secretion of its product?" and "how is information encoded in electrical activity?"^{[citation needed]}[It appears that this is a primary source observation.]

Experimental Techniques

Since the original experiments by Geoffrey Harris investigating the communication of the hypothalamus with the pituitary gland, much has been learned about the mechanistic details of this interaction. Various experimental techniques have been employed. Early experiments relied heavily on the electrophysiology techniques used by Hodgkin and Huxley. Recent approaches have incorporated various mathematical models to understand previously identified mechanisms and predict systemic response and adaptation under various circumstances.

Electrophysiology

Electrophysiology experiments were used in the early days of neuroendocrinology to identify the physiological happenings in the hypothalamus and the posterior pituitary especially. In 1950, Geoffrey Harris and Barry Cross outlined the oxytocin pathway by studying oxytocin release in response to electrical stimulation. In 1974, Walters and Hatton investigated the effect of water dehydration by electrically stimulating the supraoptic nucleus-- the hypothalamic center responsible for the release of vasopressin. Glenn Hatton dedicated his career to studying the physiology of the Neurohypophyseal system, which involved studying the electrical properties of hypothalamic neurons. Doing so enabled investigation into the behavior of these neurons and the resulting physiological effects. Studying the electrical activity of neuroendocrine cells enabled the eventual distinction between central nervous neurons, neuroendocrine neurons, and endocrine cells.

Mathematical Models

Hodgkin-Huxley Model

The Hodgkin-Huxley model translates data about the current of a system at a specific voltage into time-dependent data describing the membrane potential. Experiments using this model typically rely on the same format and assumptions, but vary the differential equations to answer their particular questions. Much has been learned about vasopressin, GnRH, somatotrophs, corticotrophs, and lactotrophic hormones by employing this method.

Integrate-and-Fire Model

The integrate-and-fire model aims for mathematic simplicity in describing biological systems. It describes on the threshold activity of a neuron. By focusing only on this one aspect, the model successfully reduces the complexity of a complicated system, however it ignores the actual mechanisms of action and replaces them with functions-- rules governing how the output of a system relates to its input. This model has been used to describe the hormones released to the posterior pituitary gland-- oxytocin and vasopressin.

Functional or Mean Fields Model

The functional or mean fields model relies on the premise "simpler is better". It strives to reduce the complexity of modelling multi-faceted systems by using a single variable to describe an entire population of cells. The alternative would be to use a different set of variables for each population. When attempting to model a system where multiple populations of cells interact, using several sets quickly becomes overcomplicated. This model has been used to describe several systems, especially involving the reproductive cycle (menstrual cycles, luteinizing hormone, prolactin surges). Functional models also exist to represent cortisol secretion, and growth hormone secretion.