Reduced Growth Hormone Secretion Prolongs Puberty But Does Not Delay the Developmental Increase in Luteinizing Hormone in the Absence of Gonadal Negative Feedback1

Abstract

Previous studies have shown that the growth hormone (GH) axis is important for timing the later stages of puberty in female monkeys. However, it is not clear whether these growth-related signals are important for the initiation of puberty and early pubertal events. The present study, using female rhesus monkeys, used two approaches to answer this question. Experiment 1 tested the hypothesis that reduced GH secretion would blunt the rise in nocturnal LH secretion in young (17 mo; n = 7) but not older adolescent ovariectomized females (29 mo; n = 6). Reduced GH secretion was induced by treating females with the sustained release somatostatin analogue formulation, Sandostatin LAR (625 microg/kg). Morning (0900-0930 h) and evening (2200-2230 h) concentrations of bioactive LH were higher in older adolescent compared to young adolescent females. However, diurnal concentrations were not affected by the inhibition of GH secretion in either age group when compared to the placebo-treated, control condition. Experiment 2 tested the hypothesis that reduced GH secretion induced in young juvenile females would delay the initial increase in nocturnal LH secretion and subsequent early signs of puberty. In order to examine this hypothesis, puberty in control females (n = 7) was compared to those in which puberty had been experimentally arrested until a late adolescent age (29 mo) by the use of a depot GnRH analogue, Lupron (750 microg kg(-1) mo(-1); n = 7). Once the analogue treatment was discontinued, the progression of puberty was compared to a group treated in a similar fashion but made GH deficient by continuous treatment with Sandostatin LAR (n = 6). Puberty occurred as expected in control females with the initial rise in evening LH at 21 mo, menarche at 22 mo, and first ovulation at 30 mo. As expected, Lupron arrested reproductive maturation, but elevations in morning and evening LH and menarche occurred within 2 mo of the cessation of Lupron in both Lupron and Lupron-GH-suppressed females. In contrast, first ovulation was delayed significantly in the Lupron-GH-suppressed females (41 mo) compared to the Lupron-only females (36 mo). These data indicate that within this experimental model, reduced GH secretion does not perturb the early stages of puberty but supports previous observations that the GH axis is important for timing the later stages of puberty and attainment of fertility. Taken together, the data indicate that factors that reduce GH secretion may have a deleterious effect on the completion of puberty.

Gene-Environment Interactions, Not Neonatal Growth Hormone Deficiency, Time Puberty in Female Rhesus Monkeys1

“…What the data do indicate is that the lower serum GH concentrations throughout development produced by Lupron and Sandostatin postnatal do not adversely affect growth or eventual puberty. Although significantly lower than controls, these GH concentrations were not suppressed to the degree of those produced in other monkey models of juvenile GH deficiency that do result in a slowing of growth and a delay in first ovulation [10,56]. Taken together, these data suggest there may be a critical lower limit of GH secretion below which normal growth and puberty is compromised.…”

“…Lup females (n ¼ 6) were weighed and injected subcutaneously with 750 lg/kg Depot Lupron every 25 days until the last treatment at 225 days of age. This dose effectively blocks activation of the pituitary-gonadal axis in juvenile female monkeys [56,57] and arrests precocious puberty in girls [58]. GHx females (n ¼ 6) were weighed and injected intramuscularly with 625 lg/kg Sandostatin LAR (Sandoz Pharmaceuticals) every 25 days until the last treatment at 225 days of age.…”

“…GHx females (n ¼ 6) were weighed and injected intramuscularly with 625 lg/kg Sandostatin LAR (Sandoz Pharmaceuticals) every 25 days until the last treatment at 225 days of age. This dose produces GH deficiency in juvenile female monkeys [56]. Animals received their respective treatments every 25 days, with the last treatment given at 225 days or 7.4 mo of age.…”

“…Prepubertal growth or factors that regulate growth have long been considered important for timing maturation of the reproductive axis. Indeed, changes in hormones that either stimulate skeletal or muscular growth [8][9][10][11][12] or increase in response to accumulation of body fat [13][14][15] explain some of the variation in puberty timing, suggesting that these can act centrally to influence systems regulating developmental increases in GnRH [16,17].…”

Metabolic and reproductive consequences of the serotonin transporter promoter polymorphism (5-HTTLPR) in adult female rhesus monkeys (Macaca mulatta)

“…''Height'' was determined on the basis of a measurement made from the top of the head to the bottom of the heel while animals were positioned supine with their legs fully straightened. The measurement was taken by two individuals using MHC vernier calipers and the mean of these was used as that animal's height index [41]. Sagittal abdominal diameters (SAD) were also obtained while females were anesthetized and in a supine position.…”