View source for Models of hypothalamus

==The Hypothalamus and the Pituitary Gland==

The [[hypothalamus]] is the region of the brain that controls [[hormone]] release, and is thus part of the [[neuroendocrine system]]. The [[pituitary gland]] is closely allied with the hypothalamus, both functionally and physically. Some hypothalamic [[neuron]]s project directly to the [[Pituitary Gland|neural lobe]] of the pituitary. Others project to the [[median eminence]], where they connect with blood vessels that supply the pituitary. In either case, the hypothalamic neurons influence cells of the pituitary, either upregulating or downregulating their activity. Hormones secreted from the pituitary in turn influence neurons throughout the brain (including the hypothalamus), and endocrine glands located in other parts of the body such as the adrenal, pineal, thyroid, parathyroid, thymus, heart, stomach, duodenum, pancreas, testes, ovaries, and placenta.
[[Image:hypo_pit.jpg|left|thumb|500px|Connections from the hypothalamus to pituitary, and some targets of pituitary hormones.]]

The pituitary gland has two well defined regions: the posterior pituitary (or neurohypophysis), and the anterior pituitary (or adenohypophysis). The posterior pituitary is innervated by the terminals of oxytocin and vasopressin neurons which originate in the hypothalamus and which synapse directly on capillaries that fenestrate the pituitary. However the anterior pituitary does not receive direct neural input from the brain, but instead is connected to the hypothalamus through a vascular network called the hypophyseal portal system. Specific releasing factors are secreted into this vascular system by the hypothalamus and subsequently act upon their target cells in the anterior pituitary.

The anterior pituitary gland contains several cell types, each secreting a specific hormone:
* '''[[Corticotrophs]]''' secrete adrenocorticotropic hormone (ACTH), which stimulates the synthesis and release of [[glucocorticoids]] from the [[adrenal cortex]]. 
* '''[[Somatotrophs]]''' secrete [[growth hormone]], which promotes the growth of most cells in the body. 
* '''[[Lactotrophs]]''' secrete [[prolactin]], which initiates milk synthesis in the [[mammary glands]] and has many other roles related to reproduction and parental behavior.
* '''[[Gonadotrophs]]''' secrete two hormones, [[luteinizing hormone]] (LH) and [[follicle stimulating hormone]] (FSH). In the female, LH stimulates ovulation and the formation of [[corpora lutea]] in the [[ovary]]. In the male, LH stimulates the [[Leydig cells]] to secrete [[androgens]] such as [[testosterone]]. FSH promotes the development of [[gametes]] and the secretion of [[gonadal hormones]] in males and females.
* '''[[Thyrotrophs]]''' secrete [[thyroid stimulating hormone]] (TSH), which stimulates the synthesis and release of [[thyroxine]] and [[triiodothyronine]] from the [[thyroid gland]].

All of these cells are electrically excitable, and possess many of the same membrane currents as do neurons, however they do not have dendritic or axonal projections. In common with the neural release of neurotransmitter, hormonal secretion from pituitary cells often arises as a consequence of electrical activity. That is, increased electrical activity raises the intracellular levels of calcium and cAMP, and this stimulates secretion of the hormone. Hormone release can also occur as a consequence of calcium release from intracellular stores such as the endoplasmic reticulum. Furthermore most pituitary cells, and many neuroendocrine cells, discharge bursts of action potentials and one of the main contributions that modelling has made is to help understand the mechanisms by which these cells burst.

Secretion from both the hypothalamus and the pituitary is pulsatile (Knobil 1980; Brabant et al. 1986). This means that during homeostasis, release is not constant, but rather occurs in intermittent boluses that repeat periodically. The cycle time of this pulsatility can range from minutes (e.g. the release of oxytocin during lactation) to an hour (e.g. GnRH secretion) to a day (diurnal vasopressin release). It is often the case that the hormone rhythm is composed of several frequencies.
 
For some endocrine cells (e.g. oxytocin and GnRH neurons) each bolus is generated by the entire population firing bursts of action potentials in close synchrony. However, for others, typically those with slower cycle times (e.g. vasopressin neurons), pulsatility is mediated by a general increase in firing rate across the population, but there is little or no synchronization of individual firing times. Therefore it would appear that (i) all endocrine and neuroendocrine cells have intrinsic rhythmic properties; (ii) there is some form of communication between cells even though populations are spread bilaterally in the hypothalamus; and (iii) the rhythm is entrained to that of the suprachiasmatic nucleus.

What is the purpose of pulsatile hormone secretion? In a mathematical study, Li and Goldbeter (1989) demonstrated that if the target cell has a desensitizing receptor, as is typically the case, then hormone released in a constant manner is not optimally effective at stimulating the target cell. A periodic release pattern may not, however, be any better than a constant release pattern. What is important is the duty cycle of the periodic release pattern. That is, the ratio of hormone release duration to inter-release duration during each periodic cycle. Li and Goldbeter demonstrated that there is an optimal duty cycle for which the effect of the pulsatile hormone release has maximum impact on the target cell. The optimal duty cycle depends on the rate at which the hormone receptor desensitizes and resensitizes.