Part 1: Image-Mapped Tutorial
Part 2: Matching Self-Test
Part 3: Multiple-Choice Self-Test
1 - Hypothalamic Releasing and Inhibiting Hormones
The hypothalamus produces six releasing hormones or factors (all peptides) that stimulate or inhibit the release of six hormones produced within the anterior pituitary. The term "hormone" is reserved for the hypothalamic, releasing substances that have been isolated via painstaking research. There are three verified hypothalamic hormones, the thyrotropin-releasing hormone, gonadotropin-releasing hormone, and the follicle-stimulating hormone. The term "factor" is used for the releasing substances that have yet to be verified experimentally. There are three hypothalamic releasing factors, the corticotropin-releasing factor, prolactin-releasing factor, and the somatotropin-releasing factor. The thyrotropin-releasing hormone stimulates the release of thyrotropin or the thyroid-stimulating hormone (TSH) from the pituitary gland. The gonadotropin-releasing hormone controls the release of the two gonadotropin hormones, the luteinizing hormone (LH) and the follicle-stimulating hormone (FSH). The corticotropin-releasing factor controls the release of the adrenocorticotrophic hormone (ACTH) from the pituitary gland. The prolactin-releasing factor controls the release of prolactin from the pituitary gland. Finally, the somatotropin-releasing factor controls the release of the somatotropic hormone or growth hormone. The actions of the target hormones stimulated by the hypothalamic and the pituitary factors and hormones are covered in Tutorial 35.
The release of substances from the hypothalamus is controlled via feedback that is provided by circulating levels of the target hormones. The primary feedback mechanism at work is negative feedback, whereby increased levels of the target hormones result in a decrease in the release of substances from the hypothalamus and decreased levels of the target hormones result in an increase in the release of hypothalamic substances. Negative feedback serves to maintain homeostatic balance. Positive feedback occurs on a less frequent basis. In positive feedback, decreased levels of the target hormones cause a continued suppression of the release of hypothalamic substances and increased levels of the target hormones cause additional increases. Research suggests that the switch from negative feedback mechanisms to positive feedback mechanisms may underlie the hormonal surges that trigger ovulation in the menstrual cycle of females.
2 - Hypothalamopituitary Portal System
The releasing hormones and factors of the hypothalamus are secreted from the nuclei where they are synthesized into the veins of a capillary bed. This capillary bed forms a portion of the hypothalamopituitary portal system. The portal veins of this system carry the releasing substances through the pituitary stalk to another capillary bed located in the anterior pituitary. The hypothalamic releasing hormones and factors leave the veins of the second capillary bed and then affect the activity of the anterior pituitary neurons. The hormones produced by the anterior pituitary neurons in response to the hypothalamic releasing factors are then secreted into this same portal system. The portal system connects to the general circulatory system, whereby the hormones are distributed throughout the body.
3 - Modulation of Anterior Pituitary Hormone Release
The anterior pituitary produces and secretes: 1) adrenal-corticotropic hormone (ACTH, which stimulates the adrenal cortex), 2) thyroid-stimulating hormone (TSH, which stimulates the thyroid gland to produce and secrete thyroxine and triiodothyrine), 3) luteinizing and follicle-stimulating hormone (LH and FSH, which stimulate the gonads or ovaries and testes to produce the sex steroid hormones including estrogen, progesterone, and testosterone), 4) prolactin (which stimulates the mammary glands), and 5) somatotropin or growth hormone (GH, which promotes metabolic activity resulting in growth and repair throughout the body). Additional information about the actions of these endocrine hormones and the glands that produce and secrete them is provided in Tutorial 35.
The secretion of hormones from the anterior pituitary is controlled via feedback mechanisms in response to levels of hormones or factors released from the hypothalamus, and circulating levels of its own hormones and those of its target endocrine glands. Hormones are typically released in surges or pulses of short duration throughout the day. Because of this pulsatile hormone release, levels of hormones in the blood stream may fluctuate widely from one minute to the next.
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Prolactin, growth hormone, and adrenocorticotrophic hormone are single chain peptides, whereas thyroid-stimulating hormone, luteinizing hormone, and prolactin are composed of two peptide chains (alpha and beta). The alpha chains are identical for all three hormones, but the beta chain differs and is responsible for the specific action of the hormone. Recent research indicates that all of the anterior pituitary hormones are released exclusively in response to the releasing factors secreted by the hypothalamus, except prolactin. Prolactin is secreted by specialized cells, called lactotrophs, in pulses occurring approximately every eight to ten minutes in the absence of external stimulation (Devost & Boutin, 1999). Therefore, the texts that identify the "prolactin-releasing factor" as the substance controlling the release of prolactin, grossly oversimplify the complex mechanisms that appear to control prolactin's release. That is, although the hypothalamus does produce a substance that appears to stimulate the release of prolactin from the pituitary gland (Hazlerigg, Hastings & Morgan, 1996), prolactin appears to be produced and released without the intervention of a hypothalamic-releasing factor. The automatic pulsatile release of prolactin from the lactotrophs of the pituitary gland is greatest at night, especially during REM sleep. Another recent discovery indicates that the secretion of both prolactin and thyroid-stimulating hormone from the pituitary is inhibited by dopamine released by the hypothalamus (Parent, 1996). Therefore, dopamine acts as both a prolactin- and thyroid-inhibiting factor.
In the early to mid-1980's several families of molecules called cytokines (growth factors) emerged from laboratory research. One of the first cytokines discovered was interleukin-1. Initial findings indicated that cytokines are synthesized by white blood cells (lymphocytes) involved in the immune response. The production of cytokines increases in response to environmental stress and infection (Elenkov, 1999). They in turn increase the production of various components needed to protect against infection. It was later discovered that cytokines are also produced by cells within the anterior pituitary gland, called folliculo-stellate cells (FS cells). FS cells do not synthesize and secrete pituitary hormones, but produce a variety of the growth factors such as fibroblast growth factor, vascular endothelial cell growth factor, and interleukin 6. In general, these growth factors stimulate hormonal secretion from the anterior pituitary gland and normal cellular growth or turnover in the gland (Renner, et. al., 1998).
The cytokines can be distinguished based on their particular physiological effects. For example, interleukin 1 activates hypothalamic-pituitary function and increases the production of norepinephrine in response to infection and environmental stress (Dunn et.al., 1999). Interleukin 1 activity also varies with levels of gonadal hormones and across the menstrual cycle (Kalra, et. al., 1998). This cytokine inhibits the luteinizing hormone surge that triggers ovulation, and may thereby prevent inopportune conception. It also triggers a mechanism underlying natural abortion, and may thereby prevent an untimely pregnancy during the course of an infection. Interleukin 6 also activates hypothalamic-pituitary function, but increases the production of serotonin and its precursor amino acid (tryptophan) in response to infection and environmental stress (Barkhudaryan & Dunn, 1999). The interleukin molecules probably exert their effects via complex processes involving both the corticotropin-releasing factor and a number of opioid peptides.
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Barkhudaryan, N. & Dunn, A.J. (1999). Molecular mechanisms of actions of interleukin-6 on the brain, with special reference to serotonin and the hypothalamic-pituitary-adrenocortical axis. Neurochemistry Research, 24(9), 1169-1180.
Devost, E. & Boutin, J.M. (1999). Autorregulation of the rat prolactin gene in lactotrophs. Molecular and Cellular Endocrinology, 158(1-2), 99-109.
Dunn, A.J., Wang, J. & Ando, T. (1999). Effects of cytokines on cerebral neurotransmission. Comparison with the effects of stress. Advanced Experimental and Medical Biology, 461, 117-127.
Elenkov, I.J., Webster,E.L., Torpy, D.J. & Chrousos, G.P. (1999). Stress, corticotropin-releasing hormone, glucocorticoids, and the immune/inflammatory response: acute and chronic effects. Annals of the New York Academy of Sciences, 875, 1-11.
Hazlerigg, D.G., Hastings, M.H. & Morgan, P.J. (1996). Production of prolactin releasing factor by the ovine pars tuberalis. Journal of Neuroendocrinology, 8(7), 489-492.
Kalra, P.S., Edwards, T.G., Xu, B., Jain, M. & Kalra, S.P. (1998). The anti-gonadotropic effects of cytokines: the role of neuropeptides. Domestic Animal Endocrinology, 15(5), 321-332.
Parent, A. (1996). Carpenter's human neuroanatomy (9th ed.). London: Williams & Wilkins.
Renner, U., Gloddek, J., Pereda, M.P., Arzt, E. & Stalla, G.K. (19980. Regulation and role of intrapituitary IL-6 production by folliculostellate cells. Domestic Animal Endocrinology, 15(5), 353-362.