Regulatory circuits of the pituitary gland

Abstract

Abstract Hormones are messengers that enable the communication among the nervous, endocrine andimmune systems, in order to maintain homeostasis. The pituitary gland produces hormones with multiple functions, including stimulation of peripheral endocrine glands, i.e. thyroid, adrenals, and gonads, of body growth, lactation, and several metabolic processes. Pituitary hormones are also playing an integrating role in the function of the immune system. According to the classic concept, the six anterior pituitary hormones, namely growth hormone (GH), prolactin (PRL), adrenocorticotropin (ACTH), thyroid stimulating hormone (TSH), and gonadotropins (FSH and LH) are produced by five pituitary cell types represented by somatotrophs, lactotrophs, corticotrophs, thyrotrophs, and bihormonal gonadotrophs. The hormone production and proliferation of pituitary cells are controlled by hypothalamic releasing and inhibiting hormones as well as peripheral target hormones. It is well established that GH, PRL, and TSH are involved in the stimulation of immune responses, whereas ACTH in the depression of immune responses. The GH production by somatotrophs is stimulated by growth hormone-releasing hormone (GHRH) and inhibited by somatostatin (SRIF), both produced by hypothalamus. GH is released into circulation and stimulates the liver and other tissues including hematopoietic cells to produce insulin-like growth factor I (IGF-I). IGF-I has a stimulation effect on the size of lymphoid organs. Pituitary PRL secretion by lactotrophs is under tonic inhibition by hypothalamic dopamine. Several candidates for PRL releasing factor (PRF) such as vasoactive intestinal peptide (VIP), thyrotropin stimulating hormone (TRH), galanin, oxytocin and prolactin-releasing peptide have been proposed, but a physiologic PRF has not been identified. TSH production by thyrotrophs is stimulated by hypothalamic TRH, and inhibited by SRIF. ACTH production by corticotrophs is stimulated by corticotropin releasing hormone (CRH), and in some species by arginin vasopressin (AVP), which is co-localized with CRH in the hypothalamus. In response to host stress, corticotrophs integrate peripheral and brain signals and release ACTH that stimulates adrenal glucocorticoid release, followed by immunosuppression. Besides hormones, pituitary cells synthesize many growth factors including cytokines known to regulate growth and differentiation of hematopoietic and inflammatory cells. They comprise interleukins, leukemia inhibitory factor, macrophage migration inhibitory factor, epidermal growth factor, transforming growth factors, fibroblastic growth factors, nerve growth factor, galanin, IGFs, activin, and inhibins. The cytokines may be released into circulation or locally acting directly on hormone producing cells and adding an additional level of pituitary control. An intrapituitary network of cytokines is induced in the acute phase of septic shock, in addition to the circulating, peripherally derived cytokines. Recently, mice lacking hormones, cytokines, or their receptors have been produced by genetic manipulation, helping to better understand their role in the cross-talk between immune and neuroendocrine system.