Pituitary hormone, function

In humans, the hypothalamic-derived protein and the hormone noncovalent complexes are packaged in neurosecretory granules, then migrate along axons at a rate of 1 4 mm/h until they reach the posterior pituitary where they are stored prior to release into the bloodstream by exocytosis (67). Considerable evidence suggests that posterior pituitary hormones function as neurotransmitters (68) vasopressin acts on the anterior pituitary to release adrenocorticotropic hormone [9002-60-2] (ACTH) (69) as well as on traditional target tissues such as kidneys. Both hormones promote other important central nervous system (CNS) effects (9,70). 

Pfizer s phase III anti-CTLA-4 antibody (Tremelimumab) trial has recently been halted as no beneficial effect over chemotherapy alone has been observed. The safety profile of the antibody is also a problem, as it may cause rash, diarrhoea, hepatitis, bowel inflammation, loss of pituitary hormone function, and hypothyroidism. 

Xenobiotic induced disruption of female fertility follows essentially the same pattern as that of the male and can be caused by changes in pituitary-hypothalamic function, primary disruption of ovarian structure or hormone secretion, or changes in the rate of hormone deactivation. In addition, there may be changes in the synthesis of estrogen induced production of the yolk protein by the liver (vitellogenesis), which in turn can lead to failure to lay down sufficient yolk in the developing oocytes. Vitellogenesis provides a valuable biomarker for endocrine dysfunction in both sexes,but is more properly considered as part of the liver function. 

Oxytocin, a nonapeptide hormone secreted by the pituitary gland, functions by stimulating uterine contraction and lactation during childbirth. Its sequence was determined from the following evidence ... 

This section of the chapter discusses FSH, LH, GH, and ACTH. FSH and LH are called gonadotropins because they influence the gonads (the organs of reproduction). GH, also called somatotropin, contributes to the growth of the body during childhood, especially the growth of muscles and bones. ACTH is produced by the anterior pituitary and stimulates the adrenal cortex to secrete the corticosteroids. The anterior pituitary hormone, TSH, is discussed in Chapter 51. Prolactin, which is also secreted by the anterior pituitary, stimulates the production of breast milk in the postpartum patient Additional functions of prolactin are not well understood. Prolactin is the only anterior pituitary hormone that is not used medically. 

Loss of other hormonal functions (i.e., LH, FSH, TSH, and ACTH) caused by massive tumor size compressing the anterior pituitary lobe. 

Although it is the dominant organ of the neural system, the brain also has an endocrine function, enabling the all-important overlap between neural and endocrine control systems. The most obvious and classically recognized hormonal function of the brain arises from the peptide hormones of the hypothalamus. The hypothalamus is intimately connected with the pituitary, producing the hypothalamic-pituitary axis. The hypothalamus is part of the brain the pituitary, although located within the skull, is not part of the brain but is part of the endocrine system. Peptide hormones from the hypothalamus influence pituitary function and thus endocrine function throughout the body. 

Figure 5.2 The Hypothalamic Pituitary Axis The hypothalamus is part of the diencephalon within the brain. The pituitary, although located within the skull, is more correctly a part of the endocrine system than the nervous system. Together, the hypothalamus and pituitary form the interface between the nervous system and endocrine system and exert control over the majority of other hormone secreting organs. Releasing and inhibiting factors permit the hypothalamus to control the pituitary. Pituitary hormones are released into the general circulation, affecting metabolic function throughout the thorax and abdomen.

Hypothalamo-pituitary function Anterior pituitary hormones Posterior pituitary hormones Adrenal cortex Adrenal medulla Thyroid Pancreas INTRODUCTION... 

Like many other neuropeptides, NT serves a dual function as a neurotransmitter or neuromodulator in the central nervous system and as a local hormone in the periphery. When administered centrally, NT exerts potent effects including hypothermia, antinociception, and modulation of dopamine neurotransmission. When administered into the peripheral circulation, it causes vasodilation, hypotension, increased vascular permeability, increased secretion of several anterior pituitary hormones, hyperglycemia, inhibition of gastric acid and pepsin secretion, and inhibition of gastric motility. It also exerts effects on the immune system. 

All the hormones produced by the anterior pituitary except prolactin (PRL) are key participants in hormonal systems in which they regulate the production by peripheral tissues of hormones that perform the ultimate regulatory functions. In these systems, the secretion of the pituitary hormone is under the control of a hypothalamic hormone. Each hypothalamic-pituitary-endocrine gland system or axis provides multiple opportunities for complex neuroendocrine regulation of growth, development, and reproductive functions. 

The occurrence of a variety of neuropeptides in the brain has been discussed in Section A. The first of these to be discovered811 was the 11-residue substance P (Table 30-4), which was isolated in 1931. Like other neuropeptides it may function either as a transmitter or neuromodulator or perhaps both. Substance P, as well as many other neuropeptides, has been localized to specific neurons. Along with somatostatin, CCK, and enkephalins, it is found in high concentrations in the basal ganglia. Enkephalin and substance P are also found in specific neural elements in the visual system of lobsters.812 In some cases a neuron contains both synaptic vesicles containing a major neurotransmitter and also vesicles containing a peptide or other cotrans-mittor. The peptide pituitary hormones ACTH, MSH, and vasopressin as well as the hypothalamic neurohormones may have effects on learning and behavior.813... 

The neurotransmitter histamine (HA) exerts several functions in the hypothalamus [1-2] including an involvement in the neuroendocrine regulation of pituitary hormone secretion [3]. HA has no effect directly at the level of the pituitary gland, but influences the secretion of anterior pituitary hormones either by an exerted e.g. in the paraventricular nucleus (PVN) on other central transmitters or hypothalamic regulating factors, which subsequently regulate the release of anterior pituitary hormones. In addition, HA acts on the supraoptic nucleus (SON) in the hypothalamus where the posterior pituitary hormones are synthesized and thereby exerts a direct effect on the release of the posterior pituitary hormones. Immunohistochemical studies have revealed that the histaminergic neurons, which originate in the tuberomammillary nuclei of the posterior hypothalamus, densely innervate most of the hypothalamic areas involved in the neuroendocrine control of pituitary hormone secretion [4-5]. Within the last two decades the effect of HA on pituitary hormone secretion have been explored in several studies and it has been... 

Bosl GJ, Bajorunas D. Pituitary and testicular hormonal function after treatment for germ cell tumours. Int J Androl 1987 10(l) 381-4. 

Other Hormones. Pituitary hormones regulate the function of many other endocrine glands, and hypophysectomy in male rats results in a decrease in the activity of xenobiotic metabolizing enzymes. Administration of adrenocorticotropic hormone (ACTH) also results in a decrease of those oxidative enzyme activities that are gender dependent. In contrast, ACTH treatment of female rats causes an increase in aminopyrine /V-dcmcthylasc but no change in other activities. 

Control of thyroid function via thyroid-pituitary feedback is also discussed in Chapter 37 Hypothalamic Pituitary Hormones. Briefly, hypothalamic cells secrete thyrotropin-releasing hormone (TRH) (Figure 38-3). TRH is secreted into capillaries of the pituitary portal venous system, and in the pituitary gland, TRH stimulates the synthesis and release of thyroid-stimulating hormone (TSH). TSH in turn stimulates an adenylyl cyclase-mediated mechanism in the thyroid cell to increase the synthesis and release of T4 and T3. These thyroid hormones act in a negative feedback fashion in the pituitary to block the action of TRH and in the hypothalamus to inhibit the synthesis and secretion of TRH. Other hormones or drugs may also affect the release of TRH or TSH. 

Secretion of adrenocortical steroids is controlled by the pituitary release of corticotropin (ACTH). Secretion of the salt-retaining hormone aldosterone is primarily under the influence of angiotensin. Corticotropin has some actions that do not depend upon its effect on adrenocortical secretion. However, its pharmacologic value as an anti-inflammatory agent and its use in testing adrenal function depend on its secretory action. Its pharmacology is discussed in Chapter 37 Hypothalamic Pituitary Hormones and will be reviewed only briefly here. 

GnRH and its analogs (nafarelin, buserelin, etc) have become important in both stimulating and inhibiting ovarian function. They are discussed in Chapter 37 Hypothalamic Pituitary Hormones. 

In general, secretion of hormones does not occur at a constant rate. In some cases, secretion is pulsatile, occurring in short bursts, as for many pituitary hormones. The biochemical basis of this pulsatile release is not fully understood, but the release pattern may have profound effects on hormone function, i.e., the pulsatile administration of luteinizing hormone releasing hormone (LHRH) stimulates the release of LH by the pituitary, whereas the constant infusion of the same amount of hormone per unit time has the opposite effect. 

Explain the arrangement of the hypothalamus-pituitary hormone system, including the function of hypothalamic release and release inhibitory factors tropic and nontropic hormones elaborated by the anterior, intermediary, and posterior pituitary their chemical natures and their effects on target tissues. Understand the short- and long-loop control mechanisms for hormone secretion. 

The changes in base-line hormone secretion are useful for interpretation of drug effects, it is often advisable to include dynamic function tests based on stimulation of pituitary hormone secretion, or of gonadal and adrenal hormone secretion. Examples for pituitary testing have been mentioned above and secretion. Typical pituitary function tests are the TRH test for TSH secretion, the LHRH test for secretion of FSH and LH, and the mono iodo-tyrosine (MIT) test for prolactin secretion. Synthetic CRF may be injected to stimulate secretion of corticotropin (ACTH), more frequently the injection of corticotropin is used to stimulate the adrenal directly. At the target organ level, similar... 

Optional parameters of hypothalamic-pituitary function to be determined are the hypothalamic content of CRH, and the anterior pituitary content of ACTH (group means and standard deviation). Final data may be calculated as hormone content per mg or gram of organ tissue (pituitary hormone contents), or as hormone content per tissue equivalent (hypothalamic fragments). 

---