Control of the Onset of Puberty, 1994

The Fourth International Conference on the Control of the Onset of Puberty was held at the University of Pittsburgh Medical Center from September 29 to October 1, 1994 with over 200 neurobiologists and physicians in attendance. The major themes of the conference were 1) the neurobiology of GnRH pulsatility, 2) molecular and cellular biology of the GnRH neuron, 3) ontogeny of the GnRH neuronal network, 4) morphological concomitants of the pubertal activation of pulsatile GnRH release, 5) treatment of central precocious puberty, 6) neuronal and glial regulation of the pubertal activation of GnRH release, and 7) control systems modulating prepubertal hiatus in pulsatile GnRH release. Among the conference highlights of interest to andrologists were the following.

A historical overview of the developmental biology of GnRH and gonadotropin secretion in humans and in sheep by Dr. Melvin M. Grumbach (USA) began the conference. Evidence was also presented that nitric oxide synthetase increased GnRH release in the GT1-7 GnRH-producing cell line. Dr. Dionysia Theodosis (France) introduced the topic of pulsatility in neuroendocrine systems by describing the synaptic remodeling (plasticity) of the supraoptic nucleus (SON) of the rat during lactation. Specifically, glial covering of neurons declines, and GABAergic terminals are increased perhaps by oxytocin.

Dr. Frederick Wu (U.K.) studied LH secretion in normal prepubertal boys using a sensitive 2-site immunoassay. He showed that most boys in midchildhood exhibit nocturnal LH pusatile release, and that LH pulse frequency is increased in agonadal boys, indicating that the testis controls GnRH secretion during childhood. Later in the meeting, Dr. Richard Stanhope (U.K.) reviewed pubertal changes in girls and suggested that increased responsiveness to GnRH explains the earlier onset of puberty in girls than boys. Dr. Richard I. Weiner (USA) described the GT-1 GnRH-producing neuronal cell line. These cells form a network in vitro, and appear to exhibit coordinated GnRH secretion which is increased by forskolin or dopamine, and decreased by vasopressin or PRL.

Dr. Margaret Wierman (USA) reviewed the structure of the GnRH gene. She illustrated how transient transfections of GnRH-luciferase constructs identify regions of the distal promotor which are important for tissue specificity and basal promotor activity. Estrogens, progestins, phorbol esters and the transcription factor cFos each suppressed GnRH gene transcription. Dr. William Wetsel (USA) discussed processing of the GnRH prohormone by various enzymes in GT-1 cells, and Dr. W.R. Crowley (USA) discussed the stimulatory effect of neuropeptide Y (NPY) on GnRH release. The fetal migration of GnRH neurons from the olfactory placode to the hypothalamus, and the role of NCAM and other adhesion molecules in this process were discussed by Dr. Donald Pfaff (USA). Dr. Jeanne-Pierre Hardelin (France) described point mutations in the terminal portion of Xp human chromosome which appear to explain the genetic basis of some cases of Kallmann's syndrome, and Dr. William F. Crowley Jr. (USA) described how clinical studies of GnRH deficient men treated with pulses of GnRH further the understanding of the control of gonadotropin secretion by GnRH and testicular hormones in men.

Dr. Michael Merzenich (USA) reviewed principles of plasticity in the brain. Neurotransmitter synapses which contact GnRH neurons in rats and monkeys were discussed by Drs. Csaba Leranth (USA) and Paul Goldsmith (USA), respectively. Dr. Ann Silverman (USA) described the movement into the habenula of mast cells which stain for GnRH during sexual maturation in the rain dove. Dr. Ayesh Perera (USA) presented the result of experiments designed to determine whether the neuroendocrine changes of puberty in male rhesus monkeys are associated with changes in synaptic input to GnRH neurons. So far, no differences between GnRH neurons in immature and adult animals have been identified. Precocious puberty due to lesions in the central nervous system was reviewed by Dr. Selma Siegel (USA), and Drs. Henriette Delamarre van de Wall (The Netherlands) and Gordon Cutler (USA) discussed idiopathic central precocious puberty. The conservative management of hypothalamic hamartomas causing precocious puberty was stressed.

Metabolic signals regulating GnRH secretion in lambs and primates were discussed by Drs. David Bucholtz (USA) and Judy Cameron (USA). In lambs, glucose deprivation or 2-deoxyglucose, which interferes with intracellular glucose metabolism, reduces LH secretion. On the other hand, either mixed nutrients, dextrose or a protein/fat mixture restores LH pulsatile release which is suppressed by fasting in male monkeys.

The adverse effects of the human diseases cystic fibrosis, glycogen storage disease type 1 and diabetes mellitus on growth and pubertal maturation were discussed by Dr. Margaret MacGillivray (USA).

The final talk by Dr. Gerald Theintz (Switzerland) described the delay in growth and puberty which is often observed in competitive gymnasts or swimmers.

Stephen J. Winters, USA