Hormone Ontogeny in the Ovine Fetus. XI. The Serotoninergic Regulation of Growth Hormone and Prolactin Secretion*

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Abstract
To investigate the development of serotonin-mediated GH and PRL release in the ovine fetus and neoriate, we administered 5-hydroxytryptophan (5-HTP; 20 mg/kg, iv) to 11 chronically catheterized fetuses (84–134 days old; term gestation, 147 days) and 10 infant lambs. In fetuses less than 110 days gestation (n = 4), the concentration of plasma GH rose from 101 ± 9 to 334 ± 31 ng/ml after 5-HTP (P < 0.001). The response in fetuses older than 110 days was less (P < 0.01); the mean concentration of GH rose from 127 ± 26 to 172 ± 34 ng/ml (P < 0.01). In infant lambs with lower basal GH concentrations, a GH rise comparable to that in late gestation was observed (from 6.5 ± 0.6 to 45 ± 12 ng/ml). There was a negative correlation between the incremental GH response to 5-HTP and postconceptual age (P < 0.01). 5-HTP failed to induce a PRL response in four fetuses less than 110 days old; the mean basal concentration of PRL was 10.7 ng/ml in this group. In older fetuses (121–134 days old), PRL rose from 40 ± 8 to 69 ± 12 ng/ml (P < 0.01). A greater response (P < 0.01) was seen in infant lambs, where PRL rose from 36 ± 7 to 155 ± 21 ng/ml (P < 0.001). There was a positive correlation (P < 0.01) between the PRL response to 5-HTP and postconceptual age. Results qualitatively similar to those obtained with 5-HTP were observed after the administration of fluoxetine, a serotonin reuptake inhibitor (7.5 mg/kg, iv), to four fetuses and two lambs. These results, considered together with other neuropharmacological studies in the ovine fetus, suggest that 5-HTP is acting via serotoninergic mechanisms on both GH and PRL secretion. The progressive decrease in GH responsiveness with advancing maturation is postulated to represent the development of counteracting inhibitory hypothalamic regulation of GH secretion. The development of the serotoninergic stimulation of PRL-secretion occurs later in gestation than the development of dopaminergic and TRH-mediated PRL regulation and is consistent with incomplete maturation of hypothalamic function in late gestation. The discordance between GH and PRL responses to 5-HTP and fluoxetine suggests that separate serotoninergic pathways, which mature independently, influence these two hormones.