**1. Introduction**

Growth hormone (GH) is produced mainly in the anterior pituitary gland (AP), but its expression also takes place in many other territories, such as the brain, the gonads, retina, adrenals, where this hormone, or its derivatives formed by enzymatic cleavage, performs very diverse and specific roles, although how GH is regulated at these levels is not well known.

In the anterior pituitary gland (AP), GH is the most abundant hormone, and it is synthesized in eosinophilic cells, the somatotrophs developed due to the action of the transcription factor Prop-1 (homeobox protein prophet of Pit-1), whose expression leads to the pituitary development of Pit-1-specific lineages. The Pit-1 t transcription factor determines the specific cellular expression of GH (and also prolactin (PRL) and thyroid-stimulating hormone (TSH)).

GH can be found in the pituitary as early as 8 weeks of fetal development, being a key factor for the development and maturation of multiple organs and tissues,

#### **Figure 1.**

*Changes in growth velocity throughout life. Note that when puberty approaches and sex steroids increase, they act on the synthesis and release of pituitary GH, so the growth velocity increases with respect to childhood. However, from the end of puberty, GH secretion progressively decreases with aging.*

such as the brain. This fetal GH does not seem to play any role in the growth of the fetus, despite the high growth velocity during the fetal period. In fact, anencephalic fetuses are of normal height at birth. A high growth rate also occurs after birth, up to 6–10 months of age, after which growth slows down; these changes after birth are shown in **Figure 1**.

Growth hormone secretion is pulsatile in nature; this is related to the optimal induction of physiological effects at the peripheral level: target tissues for GH appear to be more sensitive to the frequency at which this hormone arrives during a period of time than to the total amount of GH secreted during a similar period [1]. A clear pulsatility of GH only appears after birth; the majority of the GH pulses are associated with slow wave sleep, a period in which the amplitude of GH secretion reaches the maximum [2]. However, sleep processes do not appear to exert a predominant influence on GH release, since when sleep and circadian processes are misaligned, the blunting of the sleep-related GH pulse is counteracted, as in individuals deprived of sleep, by a compensatory mechanism that promotes GH pulses during wakefulness [3].

GH secretion is sexually dimorphic from the puberty, due to gender-related free estradiol (fE2) levels in the brain [4]. In humans, plasma fE2, but not testosterone (T), levels were shown to be strongly correlated with total and pulsatile GH release rates [5]. However, it cannot be ruled out whether there is an imprinting effect of sex steroids on the hypothalamic structures that govern the underlying hypothalamicsomatotrophic rhythm (HSR), as occurs in rat [6]. In women, the episodic secretion of GH is more frequent, but of a lower amplitude, while plasma GH values during trough periods are slightly higher than in men. Therefore, the fraction of GH secreted in peak episodes is lower in women, although it changes according to the phase of the menstrual cycle once puberty is established, reaching higher values in the late follicular phase of the menstrual cycle.
