Time mode of growth hormone (GH) entry into the bloodstream and steady-state plasma GH concentrations, rather than sex, estradiol, or menstrual cyclestage, primarily determine the GH elimination rate in healthy young women and men

We have investigated whether a reduced MCR of GH in women will account for their higher serum GH concentrations premenopausally compared with those in men. To this end, we directly compared the half-life (t(1/2)) of GH and it s volume of distribution (V-o) in 13 young men and 6 comparably aged women, each evaluated at three stages of the normal menstrual cycle (viz. the ear ly follicular, late follicular, and midluteal phases). To estimate nonequil ibrium GH kinetics, each subject received octreotide pretreatment to suppre ss endogenous GH release and then 3 randomly ordered iv bolus doses of reco mbinant human GH (1, 2, and 4 mu g/kg). The resultant peak serum GH concent rations were 18 +/- 4, 36 +/- 8, and 70 +/- 9 mu g/L in six women and 17 +/ - 2, 30 +/- 4, and 84 +/- 25 mu g/L in six men (P = NS, gender contrast). C orresponding V-o values were 66 +/- 1, 71 +/- 1, and 60 +/- 1 mL/kg in wome n and 69 +/- 1, 78 +/- 1, and 73 +/- 1 mL/kg in men (P = NS). Matching mono exponential GH t(1/2), values were 7.6 +/- 0.3, 8.2 +/- 0.4, and 8.8 +/- 0. 7 min in women and 9.8 +/- 0.8, 10 +/- 1, and 9.5 +/- 1 min in men (average 1.7 min longer in men). Regression analysis disclosed no relationship betw een serum estradiol concentrations and peak serum GH levels, GH t(1/2) or V -o. GH t(1/2) values were also invariant of menstrual cycle stage, e.g. t(1 /2) values of 8.1 +/- 0.5, 9.1 +/- 1.0, and 8.1 +/- 0.4 min for the early f ollicular, late follicular, and midluteal phases, respectively. Correspondi ng normalized MCRs were 319 +/- 39 (early follicular), 340 +/- 48 (late fol licular), and 340 +/- 71 (midluteal) L/m(2).day in women and 336 +/- 50 L/m (2).day in men (P = NS), In parallel equilibrium infusion studies in men, w e administered GH by constant iv infusions for 240 min during octreotide su ppression. At doses of 0.5, 1.5, and 4.5 mu g/kg.min, steady state GH t(1/2 ) values were 9 +/- 1, 12 +/- 1, and 15 +/- 1 min (at respective steady sta te serum GH concentrations of 0.5 +/- 0.05, 2.1 +/- 0.2, and 7.5 +/- 0.5 mu g/L). In a third analysis in the same volunteers, stopping the constant iv infusions revealed t(1/2) values of GH decay from equilibrium of 26 +/- 5 and 23 +/- 2.3 min fur the two higher GH infusion rates. In a fourth paradi gm, endogenous GH t(1/2) values, as assessed in the same individuals by dec onvolution analysis of overnight (10-min sampled) serum GH concentration pr ofiles, averaged 18 +/- 1.3 min, This value was intermediate between that o f poststeady state decay and iv bolus elimination of GH. In summary, the fo regoing clinical experiments in healthy men and women indicate that 1) the nonequilibrium GH t(1/2), (body sm face area-normalized) V-o, and MCR are i ndependent of GH dose, sex, menstrual cycle stage, and serum estradiol conc entrations; 2) the GH t(1/2) calculated after iv bolus injection is signifi cantly (50%) shorter than that assessed during or after steady-state GH inf usions or endogenously (overnight) by deconvolution analysis; and 3) the de scending rank order of GH t(1/2) values in healthy volunteers is approximat ely: decay from steady state (23 +/- 2.3 min) > endogenously secreted GH (1 8 4 1.3 min) > during equilibrium infusion (15 +/- 1 min) > after bolus inf usion (9.8 +/- 0.8 min). We thus conclude that for any given body surface a rea, the elimination properties of GH in men and women reflect predominantl y the time mode of hormone entry into the circulation, rather than gender, menstrual cycle stage, or prevailing serum estradiol concentration. Accordingly, differences in serum GH concentrations in premenopausal women compared to those in young men and across the normal menstrual cycle reflec t commensurate differences in pituitary GH secretion rates.