Regulatory mechanisms of growth hormone secretion are sexually dimorphic.

Sexually dimorphic growth hormone (GH) secretory pattern is important in the determination of gender-specific patterns of growth and metabolism in rats. Whether GH secretion in humans is also sexually dimorphic and the neuroendocrine mechanisms governing this potential difference are not fully established. We have compared pulsatile GH secretion profiles in young men and women in the baseline state and during a continuous intravenous infusion of recombinant human insulin-like growth factor I (rhIGF-I). During the baseline study, men had large nocturnal GH pulses and relatively small pulses during the rest of the day. In contrast, women had more continuous GH secretion and more frequent GH pulses that were of more uniform size. The infusion of rhIGF-I (10 microg/kg/h) potently suppressed both spontaneous and growth hormone-releasing hormone (GHRH)-induced GH secretion in men. In women, however, rhIGF-I had less effect on pulsatile GH secretion and did not suppress the GH response to GHRH. These data demonstrate the existence of sexual dimorphism in the regulatory mechanisms involved in GH secretion in humans. The persistence of GH responses to GHRH in women suggests that negative feedback by IGF-I might be expressed, in part, through suppression of hypothalamic GHRH.

Nocturnal growth hormone (GH) secretion is eliminated by infusion of GH-releasing hormone antagonist.

The neuroendocrine mechanisms underlying the generation of pulsatile GH secretion in humans are poorly understood. GH secretory pulses are likely to result from acute GHRH secretory episodes, acute decreases in hypothalamic somatostatin secretion, or a combination of these mechanisms. In earlier studies we demonstrated that a single i.v. bolus of a competitive GHRH antagonist [N-Ac-Tyr1,D-Arg2)GHRH-(1-29); GHRH-Ant] blocked 40% of the nocturnal GH release. Failure to more completely eliminate nocturnal GH secretion could be due to either incomplete antagonism of endogenous GHRH action by GHRH-Ant or a non-GHRH component of GH release. We subsequently investigated whether a continuous infusion of GHRH-Ant would more completely eliminate nocturnal GH secretion. Eight men were given a 400 micrograms/kg i.v. bolus of GHRH-Ant at 2300 h, followed by a 50 micrograms/kg.h i.v. infusion of GHRH-Ant between 2300-0700 h or a saline bolus followed by a saline infusion. An i.v. bolus of GHRH (1 microgram/kg) was given at 0500 h on both occasions. Blood was sampled every 10 min between 2300-0700 h. As measured by the area under the curve (AUC) from 2400-0500 h, GHRH-Ant suppressed GH secretion by an average of 89% (1795 +/- 412 vs. 164 +/- 46 micrograms/min.L; P = 0.004). The response to GHRH was suppressed by 79% (484 +/- 140 vs. 64 +/- 19 micrograms/min.L; P = 0.02). These data demonstrate that the previously observed nonsuppressible GH secretion was probably due to incomplete blockade of pituitary GHRH receptors and that all or nearly all of nocturnal GH pulsatility can be attributed to the effect of hypothalamic GHRH.

Growth hormone secretory dynamics over the menstrual cycle.

Whether GH secretion in women varies over the menstrual cycle is uncertain. Previous investigations have led to conflicting conclusions; some studies suggested that there is an estrogen mediated rise in GH during the periovulatory (PO) and luteal (L) phases whereas others indicated no change in GH axis over the cycle. Differences in conclusions could relate to heterogeneity of the study populations, GH sampling paradigms or sensitivity of the GH assays used. In order to investigate whether GH secretion varied over the cycle, 24-h GH profiles using every 10-min sampling were obtained in 6 ovulatory women during the early follicular (EF), PO and L phases of the cycle. The TSH response to TRH, GH response to GRH and fasting plasma IGF-I were measured on each occasion. There was a trend toward higher integrated GH concentration (IGHC) during the PO phase, although this difference was not statistically significant (3284+/-721 vs 4542+/-872 vs 4071+/-699 microg/min/L; EF vs PO vs L; p=0.09). Similarly, deconvolution estimated GH secretion did not vary over the cycle (p=0.56). There were no differences in GH pulse amplitude or frequency. There were no correlations between IGHC and sex steroids. Serum IGF-I was constant over the cycle (272+/-38 vs 277+/-31 vs 265+/-38 microg/L; p=0.89). The TSH response to TRH and GH response to GRH did not vary over the cycle. We concluded that the effect of changes in the ovarian steroid milieu on the GH axis during spontaneous menstrual cycles is minimal.