Sexual maturation of the hypothalamus: Pathophysiological aspects and clinical implications

Abstract

Sexual maturation in humans begins early in fetal life and culminates in adulthood when the gonads have acquired a full capacity for reproduction. It is remarkable that during this long process, the pituitary gonadal function, hence its hypothalamic control presents an alternative of activation and inhibition periods, during which the interrelations of the 3 components of the hypothalamic-pituitary-gonadal axis change gradually and inversely. The ontogeny of the hypothalamic-pituitary system, the varying activity of the reproductive endocrine system throughout sexual maturation and the developmental changes in the interrelations of the hypothalamic-pituitary-gonadal axis are reviewed: the most striking feature of human sexual development is the long inhibition of hypothalamo-pituitary function during childhood. Much indirect evidence points to the determining role of the CNS in the maturation of hypothalamic function: the occurrence of rhythms of secretion, the amplitude of secretions and peripubertal specific sleep-related nycthemeral rhythm of secretion at the onset of puberty. Despite the reality of a negative feedback control, these changes do occur independently of gonadal secretions since they are observed (qualitatively if not strictly quantitatively) in agonadal children. It is likely that neurotransmitters (dopamine, serotonine) and opiates have an inhibitory effect on Gn-RH release. But we still don't know their evolution during sexual maturation. It does not appear that melatonine plays any determinant role in the onset of human puberty. The clinical implications of our present understanding of the physiological events occurring during sexual maturation are several. Considering the major problems related to abnormal sexual maturation we will discuss successively: (1) diagnosis of hypogonadotrophic hypogonadism in early infancy; (2) differential diagnosis between premature thelarche and true sexual precocity; (3) the usefulness of endocrine investigations in the evaluation of hypothalamic-pituitary function; and (4) the new developments in the treatment of precocious puberty, delayed puberty or hypogonadism.

Male hypogonadism in cirrhosis and after liver transplantation

“…The discrimination of hypogonadotropic hypogonadism (HH) and constitutional delayed puberty (CDP) remains difficult, especially when inherited somatic abnormalities such as anosmia, midline deformities, unilateral renal agenesis or micropenis are missing [17,21,22]. Several authors [23][24][25] suggest that a basal testosterone[1.7 nmol/l has a good prognostic value in discriminating HH from CDP. In boys who reach this testosterone level, puberty has started spontaneously despite the absence of clinical signs.…”

Activation of the Hypothalamic-Pituitary-Gonadal Axis in Infancy: Minipuberty

“…The exact phase when the pituitary gonadotrophin secretion becomes dependent on the control of the hypothalamic GnRH is not fully elucidated. Vascular connections are already present at the end of the first trimester of pregnancy, but the maturation of the portal vascular system continues after this [for review, see [4]]. In anencephalic foetuses that lack the hypothalamus but have an intact pituitary, gonadotrope development is normal up to 17-18 weeks of gestation but thereafter the cells are involuted [5].…”

Male hypogonadism

“…Several authors [23][24][25] suggest that a basal testosterone[1.7 nmol/l has a good prognostic value in discriminating HH from CDP. In boys who reach this testosterone level, puberty has started spontaneously despite the absence of clinical signs.…”