{"id":{"repo_id":"edinburgh","oai_identifier":"oai:era.ed.ac.uk:1842/34524"},"canonical_url":"https://search.dev.ndltd.org/etd/edinburgh/oai:era.ed.ac.uk:1842/34524","repository":{"repo_id":"edinburgh","name":"University of Edinburgh","base_url":"https://era.ed.ac.uk/server/oai/request"},"display":{"title":"The hypothalamic-pituitary-testicular axis: studies on delayed puberty and infertility","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Wu, Frederick Chung Wei"],"institution":"The University of Edinburgh","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":1983,"date_issued":"1983","date_published":"1983","updated_at":"2026-07-24T02:14:11Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1842/34524","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Wu, Frederick Chung Wei"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2019-02-15T14:27:52Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2019-02-15T14:27:52Z"]},{"key":"dc:date.issued","label":"Date","values":["1983"]},{"key":"dc:publisher","label":"Institution","values":["The University of Edinburgh"]},{"key":"dc:type","label":"Dc Type","values":["Thesis or Dissertation"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["MD Doctor of Medicine"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1842/34524"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.","In infertile patients, an inverse relationship between FSH and sperm count or the severity of germ cell depletion in testicular biopsies was confirmed. The application of FSH measurements to the assessment of 100 infertile patients was evaluated. Elevated FSH in those with sperm density under 5 million /ml indicated severe germ cell atrophy. The use of GnRH stimulation and multiple measurements of basal gonadotrophins and testosterone conferred no advantage. In patients with elevated FSH, circulating oestradiol, oestrone and oestrone sulphate were significantly raised. There was preliminary evidence that the oestrogen excess resulted from testicular secretions of oestradiol. Oestrone sulphate was not secreted by the testis, being derived from unconjugated precursors - oestradiol and oestrone. The pathophysiological significance of these findings in male infertility and their relevance to normal intratesticular control mechanisms were discussed.","In conclusion, the development and control of adult testicular functions are dependent on a background of pulsatile LH stimulation against which the complex interactions between FSH, Sertoli and Leydig cells ensure a continuous maturation of spermatogonia and the optimal production of testicular steroids."]},{"key":"dc:title","label":"Title","values":["The hypothalamic-pituitary-testicular axis: studies on delayed puberty and infertility"]}]}],"canonical_facts":{"dc:creator":["Wu, Frederick Chung Wei"],"dc:date.accessioned":["2019-02-15T14:27:52Z"],"dc:date.available":["2019-02-15T14:27:52Z"],"dc:date.issued":["1983"],"dc:description.abstract":["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.","In infertile patients, an inverse relationship between FSH and sperm count or the severity of germ cell depletion in testicular biopsies was confirmed. The application of FSH measurements to the assessment of 100 infertile patients was evaluated. Elevated FSH in those with sperm density under 5 million /ml indicated severe germ cell atrophy. The use of GnRH stimulation and multiple measurements of basal gonadotrophins and testosterone conferred no advantage. In patients with elevated FSH, circulating oestradiol, oestrone and oestrone sulphate were significantly raised. There was preliminary evidence that the oestrogen excess resulted from testicular secretions of oestradiol. Oestrone sulphate was not secreted by the testis, being derived from unconjugated precursors - oestradiol and oestrone. The pathophysiological significance of these findings in male infertility and their relevance to normal intratesticular control mechanisms were discussed.","In conclusion, the development and control of adult testicular functions are dependent on a background of pulsatile LH stimulation against which the complex interactions between FSH, Sertoli and Leydig cells ensure a continuous maturation of spermatogonia and the optimal production of testicular steroids."],"dc:identifier.uri":["http://hdl.handle.net/1842/34524"],"dc:publisher":["The University of Edinburgh"],"dc:title":["The hypothalamic-pituitary-testicular axis: studies on delayed puberty and infertility"],"dc:type":["Thesis or Dissertation"],"dc:type.qualificationlevel":["Doctoral"],"dc:type.qualificationname":["MD Doctor of Medicine"]},"updated_at":"2026-07-24T02:14:11Z"}