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P A R T 6  Drugs acting on the endocrine system

the brain led early scientists to believe that it must be the chief control gland. However, as knowledge of the endo­ crine system has grown, scientists now designate the hypothalamus as the master gland because it has even greater direct regulatory effects over the neuroendocrine system, including stimulation of the pituitary gland to produce its hormones. The anterior pituitary The anterior pituitary produces six major hormones: growth hormone (GH), adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), luteinising hormone (LH), prolactin (PRL) and thyroid-stimulating hormone (TSH, also called thyrotropin) (Table 34.2; see also Figure 34.1). These hormones are essential for the regulation of growth, reproduction and some meta­ bolic processes. Deficiency or overproduction of these hormones disrupts this regulation. The anterior pituitary hormones are released in a rhythmic manner into the bloodstream. Their secre­ tion varies with time of day (often referred to as diurnal rhythm ) or with physiological conditions such as exercise or sleep. Their release is affected by activity in the CNS; by hypothalamic hormones; by hormones of the periph­ eral endocrine glands; by certain diseases that can alter endocrine functioning; and by a variety of drugs, which can directly or indirectly upset the homeostasis in the body and cause an endocrine response. Normally, diurnal rhythm occurs when the hypothalamus begins secretion of corticotropin-releasing factor (CRF) in the evening, peaking at about midnight; adrenocortical peak response is between 6 and 9 a.m.; levels fall during the day until evening, when the low level is picked up by the hypothalamus and CRF secretion begins again.

The anterior pituitary also produces melanocyte- stimulating hormone (MSH) and various lipotropins. MSH plays an important role in animals that use skin colour changes as an adaptive mechanism. It might also be important for nerve growth and development in humans. Lipotropins stimulate fat mobilisation but have not been clearly isolated in humans. The posterior pituitary The posterior pituitary stores two hormones that are produced by the hypothalamus and deposited in the posterior lobe via the nerve axons where they are produced. These two hormones are ADH, also referred to as vasopressin and oxytocin. ADH is directly released in response to increased plasma osmolarity or decreased blood volume (which often results in increased osmolar­ ity). The osmoreceptors in the hypothalamus stimulate the release of ADH. Oxytocin stimulates uterine smooth muscle contraction in late phases of pregnancy and also causes milk release or “let down” reflex in breastfeeding women. Its release is stimulated by various hormones and neurological stimuli associated with labour and with breastfeeding. The intermediate lobe The intermediate lobe of the pituitary produces endor­ phins and encephalins, which are released in response to severe pain or stress and occupy specific endorphin- receptor sites in the brainstem to block the perception of pain. These hormones are also produced in peripheral tissues and in other areas of the brain. They are released in response to overactivity of pain nerves, sympa­ thetic stimulation, transcutaneous stimulation, guided imagery and vigorous exercise.

■■ TABLE 34.2 Hypothalamic hormones, associated anterior pituitary hormones and target organ response Hypothalamus hormones Anterior pituitary hormones Target organ response

Stimulating hormones CRH (corticotropin-releasing hormone) TRH (thyroid-releasing hormone) GHRH (growth hormone-releasing hormone) GnRH (gonadotropin-releasing hormone) PRH (prolactin-releasing hormone)

ACTH (adrenocorticotropic hormone)

Adrenal corticosteroid hormones

TSH (thyroid-stimulating hormone)

Thyroid hormone

GH (growth hormone)

Cell growth

LH and FSH (luteinising hormone, follicle-stimulating hormone)

Oestrogen and progesterone (females), testosterone (males)

Prolactin

Milk production

MSH (melanocyte-stimulating hormone)

Melanin stimulation (colour change in animals, nerve growth in humans)

Inhibiting hormones Somatostatin (growth hormone- inhibiting factor) PIF (prolactin-inhibiting factors)

Stops release of GH

Stops release of prolactin