The ability of neuronal signals to modulate the release of hypothalamic releasing hormones and control the endocrine axes is an important aspect of the endocrine axes. One significant source of neuronal input to releasing hormone-secreting neurons is the suprachiasmatic nucleus (SCN) in the hypothalamus. SCN neurons impose a daily rhythm, known as a circadian rhythm, on the secretion of hypothalamic releasing hormones and the endocrine axes they regulate (Fig. 38.3). The SCN neurons act as an intrinsic circadian clock, exhibiting a spontaneous peak of electrical activity at the same time every 24 to 25 hours, suggesting their role as an environmentally controlled clock. The 24-to 25-hour cycle of the SCN can be entrained by the normal environmental light-dark cycle, created by the earth's rotation (Fig. 38.4).

The retinohypothalamic tract carries neural input from specialized light-sensitive retinal cells, separate from rods and cones, to the SCN. Under constant conditions of light or dark, the SCN clock becomes "free running" and slightly deviates from a 24-hour cycle each day.

The pineal gland, located close to the hypothalamus, serves as a neuroendocrine link between the SCN and various physiological processes that require circadian control. It synthesizes the hormone melatonin from the neurotransmitter serotonin, with tryptophan as the precursor. N-acetyltransferase is the rate-limiting enzyme for melatonin synthesis. The activity and amount of this enzyme in the pineal gland exhibit cyclic variations, accounting for the cycling of melatonin secretion and plasma levels. The synthesis of melatonin is suppressed by light and greatly stimulated by darkness (see Fig. 38.4). Hence, melatonin may transmit the information of nighttime, regulating body functions accordingly. Melatonin feedback to the SCN during dawn or dusk may also aid in the day-night synchronization of the SCN's 24-to 25-hour clock. Apart from inducing sleep, melatonin has various other actions.
An important aspect of the endocrine axes is the ability of descending and ascending neuronal signals to modulate release of the hypothalamic releasing hormones and thereby control the activity of the axis. A major neuronal input to releasing hormone–secreting neurons comes from another region of the hypothalamus called the suprachiasmatic nucleus (SCN). SCN neurons impose a daily rhythm, called a circadian rhythm, on the secretion of hypothalamic releasing hormones and the endocrine axes that they control (
Fig. 38.3).
SCN neurons represent an intrinsic circadian clock, as evidenced by the fact that they demonstrate a spontaneous peak of electrical activity at the same time every 24 to 25 hours. The 24-to 25-hour cycle can be “entrained” by the normal environmental light-dark cycle created by the earth’s rotation, so that the periodicity of the clock appears to be environmentally controlled (
Fig. 38.4
Hormones Produced to a Significant Degree by Peripheral Conversion
LungsAngiotensinIIKidney1,25-DihydroxyvitaminD(vitaminD)Adipose,mammaryglands,otherorgansEstradiol-17β Liver,sebaceousgland,otherorgansTestosteroneGenitalskin,prostate,otherorgans5-Dihydrotestosterone(DHT)ManyorgansTriiodothyronine •Fig. 38.2 Physiologicalresponse–drivenandendocrineaxis–drivennegativefeedbackloops.Endocrine gland Pituitary gland Releasing hormone Peripheral endocrine gland Hormone Hormone Negative feedback Negative feedback Circulating component (e.g., blood glucose) Tropic hormone Physiological effects Physiological effects Hypothalamic neuroendocrine neurons Target organ(s) Target organs ENDOCRINE AXIS–DRIVEN NEGATIVE FEEDBACK PHYSIOLOGICAL RESPONSE–DRIVEN NEGATIVE FEEDBACK
Neural input is generated from specialized light-sensitive retinal cells that are distinct from rods and cones and from signals to the SCN via the retinohypothalamic tract. Under constant conditions of light or dark, however, the SCN clock becomes “free running” and slightly drifts away from a 24-hour cycle each day.
The pineal gland forms a neuroendocrine link between the SCN and various physiological processes that require circadian control. This tiny gland, close to the hypothalamus, synthesizes the hormone melatonin from the neurotransmitter serotonin, of which tryptophan is the precursor. The rate-limiting enzyme for melatonin synthesis is N-acetyltransferase. The amount and activity of this enzyme in the pineal gland vary markedly in a cyclic manner, which accounts for the cycling of melatonin secretion and its plasma levels. Synthesis of melatonin is inhibited by light and markedly stimulated by darkness (see
Fig. 38.4 ). Thus melatonin may transmit the information that nighttime has arrived, and body functions are regulated accordingly. Melatonin feedback to the SCN at dawn or dusk may also help evoke day-night entrainment of the SCN 24to 25-hour clock. Melatonin has numerous other actions, including induction of sleep.