The hypothalamic-pituitary-testicular axis: studies on delayed puberty and infertility

The functional characteristics and control mechanisms of the hypothalamic-pituitary-testicular axis were explored by examining the patterns of pituitary and testicular hormone secretion in pubertal subjects and in adults with impaired spermatogenesis. The overnight hormone profile and the pituitary response to repeated GnRH stimulation were studied on 1-4 occasions in 16 patients (mean age 16.3 ± 2.7 years) with delayed sexual development while their clinical progress was followed for a mean duration of 22.4 ± 8.5 months. Changes in testis and genital size were confirmed to be the two physical markers which correlated best with the hormonal patterns. The earliest detectable evidence of pubertal onset was an increase in frequency and amplitude of pulsatile LH secretion during nocturnal sleep. Further progress in puberty was characterized by quantitative and qualitative changes in the pattern of LH secretion resulting from the combined effects of changing frequency of hypothalamic GnRH pulses, of gonadal feedback and possibly other ill-defined central mechanisms. Heightened pituitary responsiveness to GnRH could account for the pubertal rise in LH. Since the estimated amplitude of GnRH pulsatile secretion remained constant, the increase in GnRH pulse frequency was considered to be the prime mover in the activation of pituitary- testicular functions at the onset of puberty. Thus the hypothalamic GnRH frequency modulation of the pituitary provides the basic mechanism for the neuroendocrine control of sexual maturation. The pituitary response to GnRH may be helpful in the endocrine assessment of patients with delayed puberty. In response to a single 10 pg bolus of GnRH, an LH rise of 5 u/l or more was associated with well- defined nocturnal pulsatile LH secretion in subjects who subsequently progressed through puberty spontaneously. However, in those where the GnRH- induced LH rise was under 5 u /1, it was not possible to differentiate between constitutional delayed puberty and hypogonadotrophic hypogonadism. The pubertal development of testicular functions was more closely related to the progressive increase in amplitude rather than frequency of pulsatile LH secretion. The roles of FSH and prolactin were less obvious. Exogenous GnRHinduced pulsatile LH secretion failed to stimulate testo- sterone production above the maximal levels in the morning. This implied that the pubertal Leydig cells normally function near to their maximal steroidogenïc capacity.

Grantor dc:publisher

The University of Edinburgh

Year dc:date.issued

1983

Author dc:creator

• Wu, Frederick Chung Wei

Handle dc:identifier.uri

http://hdl.handle.net/1842/34524

OAI identifier oai:identifier

oai:era.ed.ac.uk:1842/34524