The intermediate level of the endocrine axes consists of the cells of the adenohypophysis. This gland is responsible for secreting protein hormones known as tropic hormones. These include adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH), and prolactin (PRL) as listed in Table 41.1. Typically, tropic hormones bind to specific receptors on peripheral endocrine glands. As a result, pituitary tropic hormones do not directly regulate physiological responses, except for a few exceptions mentioned in Chapter 38.

The endocrine axes possess significant features. Firstly, the activity of a specific axis is usually maintained at a set point, which varies among individuals within a normal range. The set point is determined by the integration of hypothalamic stimulation and negative feedback from peripheral hormones. It's important to note that negative feedback is primarily exerted by the peripheral hormone itself on the pituitary and hypothalamus, rather than the physiological responses regulated by the endocrine axis. Consequently, if the level of a peripheral hormone decreases, secretion of hypothalamic releasing hormones and pituitary tropic hormones will increase. Conversely, as the level of peripheral hormone rises, the hypothalamus and pituitary will reduce secretion due to negative feedback. While certain nonendocrine physiological parameters may regulate some endocrine axes, these axes generally function semi-autonomously in relation to the physiological changes they produce. This configuration allows a peripheral hormone, such as thyroid hormone, to regulate multiple organ systems without these organ systems exerting competing negative-feedback regulation on the hormone. From a clinical standpoint, this partial autonomy implies that various aspects of a patient's physiology are vulnerable to any derangements that may exist within a specific axis.

Secondly, hypothalamic hypophysiotropic neurons often secrete hormones in a pulsatile manner and are influenced by daily and seasonal rhythms through central nervous system (CNS) input. Additionally, hypothalamic nuclei receive various neuronal inputs from higher and lower levels of the brain. These inputs can be visualized in Fig. 41.5.
The cells of the adenohypophysis make up the intermediate level of the endocrine axes. The adenohypophysis secretes protein hormones that are referred to as tropic hormones—adrenocorticotropic hormone (ACTH, also called corticotropin), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH), and prolactin (PRL) (see
Table 41.1). With a few exceptions, tropic hormones bind to their cognate receptors on peripheral endocrine glands. Because of this arrangement, pituitary tropic hormones generally do not directly regulate physiological responses (see
Chapter 38).
The endocrine axes have the following important features: 1.
The activity of a specific axis is normally maintained at a set point, which varies from individual to individual, usually within a normal range. The set point is determined by the integration of hypothalamic stimulation and peripheral hormone negative feedback. Importantly, negative feedback generally is not exerted by the physiological responses regulated by a specific endocrine axis but by the peripheral hormone itself acting on the pituitary and hypothalamus (see
Fig. 41.6 ). Thus if the level of a peripheral hormone drops, secretion of hypothalamic releasing hormones and pituitary tropic hormones will increase. As the level of peripheral hormone rises, the hypothalamus and pituitary will decrease secretion because of negative feedback. Although certain nonendocrine physiological parameters (e.g., acute hypoglycemia) can regulate some endocrine axes, the axes function semiautonomously with respect to the physiological changes they produce. This configuration means a peripheral hormone (e.g., thyroid hormone) can regulate multiple organ systems without these organ systems exerting competing negative-feedback regulation of the hormone. Clinically this partial autonomy means that multiple aspects of a patient’s physiology are at the mercy of whatever derangements might exist within a specific axis.
2.
Hypothalamic hypophysiotropic neurons are often secreted in a pulsatile manner and are entrained to daily and seasonal rhythms through CNS input. Additionally, hypothalamic nuclei receive a variety of neuronal inputs from higher and lower levels of the brain. These can be • Fig. 41.5 Synthesis, processing, and transport of preprovasopressin. Human ADH (also called arginine vasopressin [AVP]) is synthesized in the hypothalamic magnocellular cell bodies and packaged into neurosecretory granules. During intraaxonal transport of the granules down the infundibular process to the pars nervosa, provasopressin is proteolytically cleaved into the active hormone (AVP = ADH), neurophysin (NP), and a C-terminal glycoprotein (GP). NP arranges into tetramers that bind five AVP molecules. All three fragments are secreted from axonal termini in the pars nervosa (posterior pituitary) and enter the systemic blood. Only AVP (ADH) is biologically active. (Modified from Larsen PR et al [eds]. Williams Textbook of Endocrinology. 10th ed. Philadelphia: Saunders; 2003.)