Growth Signals and Puberty

Kelly J. Suter, Clifford R. Pohl and Mark E. Wilson

Yerkes Primate Research Center Emory University Lawrenceville, Georgia 30043

To the editor:

We would like to respond to Dr. Tony Plant’s comments on our study published in the February 2000 issue of JCEM entitled "Circulating concentrations of nocturnal leptin, growth hormone, and insulin-like growth factor-I (IGF-I) increase before the onset of puberty in agonadal male monkeys: potential signals for the onset of puberty."

We share the view of our colleague that the algorithm for day zero, applied post hoc to mean LH values obtained longitudinally from individual monkeys during development, produces merely an approximation of the age at which a pubertal mode of GnRH release had been initiated in a specific animal. However, we would point out that, because the day zero age is computed from mean hormone data and not from pulse characteristics, one of its strengths as a marker is that it shows no bias to either pulse frequency or pulse amplitude as a primary determinant of the developmental increase in hypophysiotropic drive to the gonadotrophs. Nevertheless, this highly desirable feature may not reveal with absolute accuracy when pulse characteristics that underlie the changes in mean hormone levels actually occur. Specifically, given the usual errors of estimation, one would predict that changes in whichever pulse characteristic dominates the pubertal transition should be detectable at a slightly earlier age than the calculated day zero. Indeed, as Plant (1), points out this is exactly what appeared in the LH analysis (2), which showed a trend for LH frequency to rise beginning at least 20 days prior to day zero.

We, therefore, cannot agree with our colleague in the appropriateness of using a side-by-side comparison of mean hormone values (GH or leptin) and LH pulse frequencies to make a case for concurrency rather than precedence in hormonal events. If anything, the demonstration provided in Fig. A (1) strengthens the possibility that changes in secretory patterns of these growth-promoting signals, especially GH, might indeed precede the demonstrated increase in pulsatile LH frequency. This is even more evident if one plots mean IGF-I levels from Fig. 3 of our manuscript (3) concurrent with LH pulse frequency, a comparison Dr. Plant did not provide. Nevertheless, any firm conclusions about this issue must await the outcome of further studies.

Although visually compelling, the data presented in Dr. Plant’s re-plot (Fig. A, Ref. 1) of the growth signal values (3) and the LH frequencies (2) aligned to day zero must be evaluated carefully. As reported in the original publication of the LH data (2), LH pulse frequencies prior to day zero were not significantly different from earlier prepubertal values (Ref. 2 , Fig. 4) whereas nocturnal leptin GH, and IGF-I (not replotted by Dr. Plant) were significantly higher prior to day zero compared with earlier prepubertal values (Ref. 3 ; Figs. 1 and 3).

One of us (C.R.P.) developed this algorithm but we are all well aware of it limitations. We simply employed it as a marker for the transition to puberty, consistent with the statement in the publication co-authored with Plant that the day zero age is "considered to represent the age at which a pubertal mode of GnRH release was initiated" (2).

It should be clear to all that our paper (3) is a "stepping-stone" presentation, with more to follow when further studies are completed. Most new findings are presented in this fashion, where the full impact of an initial observation remains undeveloped until further work is performed and empirically evaluated. We are, therefore, methodically charting this path and assure all, including Dr. Plant, that due caution is being exercised in the interpretation of day zero ages and their relationship to potential signals for the onset of puberty.

Received September 14, 2000.

References

  1. Plant T. Letter to the editor. J Clin Endocrinol Metab. 86:0000–0000.
  2. Suter KJ, Pohl CR, Plant TM. 1998 The pattern and tempo of the pubertal reaugmentation of open-loop pulsatile gonadotropin-releasing hormone release assessed indirectly in the male rhesus monkey (Macaca mulatta). Endocrinology. 139:2774–2783.[Abstract/Free Full Text]
  3. Suter KJ, Pohl CR, Wilson ME. 2000 Circulating concentrations of nocturnal leptin, growth hormone, and insulin-like growth factor-I increase before the onset of puberty in agonadal male monkeys: potential signals for the onset of puberty. J Clin Endocrinol Metab. 84:808–814.




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