Hypothalamic-pituitary regulatory

Cannabimimetics are also shown to affect reproductive and metabolic functions indirectly by hormonal modulation through the hypothalamic and pituitary regulatory centers. They are found to reduce serum levels of the luteinizing hormone, prolactin, growth hormone, and thyroid-stimulating hormone, and to increase corticotropin (Murphy, 1998). 

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. 

Somatostatin is a 14 amino acid peptide that is released in the gastrointestinal tract and pancreas from paracrine cells, D-cells, and enteric nerves as well as from the hypothalamus (see Chapter 37 Hypothalamic Pituitary Hormones). It is a key regulatory peptide that has myriad physiologic effects ... 

IL-6 acts on the pituitary to induce adrenocorticotropic hormone (ACTH) release and directly on the adrenal glands to produce glucocorticoids. It is known that different cytoldnes that share gpl30 as a receptor subunit induce serum amyloid A, and potentiate the induction of IL-6 and the activation of the hypothalamic-pituitary-adrenal axis by IL-1. In particular, LIF, OSM, IL-11, and cardiotrophin-1 potentiate the elevation of serum corticosterone and IL-6 levels induced by IL-1. Furthermore, the potentiation of IL-1-induced serum corticosterone levels is not a consequence of the increased serum IL-6 observed after IL-1 administration. Thus either endogenous IL-6 does not mediate IL-l-induced corticosterone increase, or its role may be fulfilled by other cytokines. This is very important in the understanding of the activation of the hypothalamic-pituitary-adrenal axis and that potentiation of acute phase protein synthesis may represent an important feedback regulatory mechanism of inflammation. ... 

Figure 50-4 The regulatory feedback loop of the hypothalamic-pituitary-growth hormone axis. Growth hormone-releasing hormone (GH-RH) acts on the pituitary to produce GH. GH acts on the liver to produce IGF-1, which together with GH modulates bone and muscle growth and differentiation. GH also has a catabolic effect on fat tissue. IGF-1 has a negative feedback effect on GH-RH and GH secretion, and SRIF attenuates the effects of GH-RH on the pituitary.

Figure 50-8 The regulatory feedback loop of the hypothalamic-pituitary-adrenal axis. CRH under the influence of neural factors and other modifiable factors that control its pulsatile and circadian secretion acts on the pituitary to produce hormone (ACTH). ACTH in turn stimulates the adrenal gland to form cortisol, aldosterone, dehydroepiandrosterone (DHEA), and androstenedione. Corticosteroids and gamma amino butyric acid (GABA) are inhibitory to CRH and ACTH release, and AVP stimulates ACTH release.

Figure 50-9 The regulatory feedback loop of the hypothalamic-pituitary-gonadal axis. Neural and sensory input from the brain elicits the release of Gn-RH. Gn-RH in turn stimulates the synthesis and release of the gonadotropins FSH and LH, which act on the gonads (ovary and testes) to elicit the ripening and ovulation of the ovary and steroidogenesis (estradiol and progesterone) in the female and spermatogenesis and testosterone production in the male. Inhibin formed by the ovaries and testes along with estradiol and testosterone negatively feeds back to the hypothalamic-pituitary axis to modulate Gn-RH, FSH, and LH release.

D5NS 5% dextrose and isotonic saline DDT dichlorodiphenyltrichloroethane DST dexamethasone suppression test GRE glucocorticoid regulatory element HPA hypothalamic-pituitary-adrenal IRMA immunoradiometric assay MRI magnetic resonance imaging... 

Further reading Malarkey, W.B. (1976). Recently discovered hypothalamic-pituitary hormones. Clin. Chem. 22, 5 Hall, R. and Gomez-Pan, A. (1976). The hypothalamic regulatory hormones and their clinical applications. In Bodansky, O. and Latner, A.L. (eds.) Advances in Clinical Chemistry. Vol. 18, p. 174. (New York Academic Press)... 

GC exert their regulatory effects on the HPA system via two types of corticosteroid receptors the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) (Reul and De Kloet 1985). GRs occur everywhere in the brain but are most abundant in hypothalamic CRH neurons and pituitary corticotropes. MRs, in contrast, are highly expressed in the hippocampus and, at lower expression levels, in hypothalamic sites involved in the regulation of salt appetite and autonomic outflow. The MR binds GC with a tenfold higher affinity than does the GR (Reul and De Kloet 1985). These findings on corticosteroid receptor diversity led to the working hypothesis that the tonic influences of corticosterone... 

The secretion of anterior pituitary hormones is controlled in part by hypothalamic regulatory factors that are stored in the hypothalamus and are released into the adenohypophyseal portal vasculature. Hypothalamic regulatory factors so far identified are peptides with the exception of dopamine. Secretion of anterior pituitary hormones is also controlled by factors produced more distally that circulate in the blood. Predominant control of hormone production may be relatively simple, as with thyroid-stimulating hormone (TSH), the production of which is primarily stimulated by thyrotropin-releasing hormone (TRH) and inhibited by thyroid hormones, or it may be complex, as with prolactin, the production of which is affected by many neurotransmitters and hormones. 

All anterior pituitary hormones are released into the bloodstream in a pulsatile manner the secretion of many also varies with time of day or physiological conditions, such as exercise or sleep. At least part of the pul-satility of anterior hormone secretion is caused by pulsatile secretion of hypothalamic regulatory hormones. Understanding the rhythms that control hormone secretion has led to better uses of hormones in therapy. 

The synthetic tetradecapeptide, either in linear or cyclized form has been shown to suppress growth hormone secretion in man (H3, P6, S8), in animals (Bll), and in isolated pituitary tissue (B8), confirming the lack of phylogenetic specificity seen with the other hypothalamic regulatory hormones. 

One important neuronal TRH control center appears to be the paraventricular nucleus, but TRH Is widely distributed in the hypothalamus and highly concentrated in the median eminence (4). One important ipactor regulating TRH production is environmental temperature. Both peripheral thermal receptors and preoptic neuronal thermal receptors monitor environmental and central body temperature these receptors modulate preoptic neuronal outflow to the paraventricular nucleus and other TRH synthesizing neurons in the hypothalamus and median eminence which. In turn, modulate TRH secretion (4). Decreasing environmental and/or core body temperature Increase TRH output and increase the tonic level of TSH release. Somatostatin (SRIF) and dopamine can inhibit TSH release by actions at the pituitary level, and these inhibitory transmitters contribute to central nervous system modulation of TSH release (4). There is evidence that serotonin may be inhibitory in the adult rat, but this does not seem to be so in other species. Norepinephrine also may be inhibitory. Glucocorticoid can inhibit TSH release at the hypothalamic level, but the mechanism is not known. The exact roles of TRH and non-TRH regulatory factors in TSH control are not clear. Administration of somatostatin antiserum to adult rats increases basal TSH levels and potentiates the TSH response to cold (19). Inhibitory factors probably also play a role in the diurnal variation in TSH secretion, in the inhibitory reactions to stress, in the variation in thyroidal activity in psychosis, etc. 

Potential modes of action of lead reproductive toxicity include disraption of the hypothalamic-pituitaiy-gonadal axis through reduced luteinizing hormone secretion and reduction in the expression of the steroidogenic acute regulatory protein (Crain et al. 2008 EPA 2012). Lead may also interfere with cation-dependent secondary messenger systems that mediate pituitary hormone release... 

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