Repetitive Stimulation of the Pituitary with Growth-Hormone-Releasing Hormone Alters the Proportion of 22 and 20 Kilodalton Human-Growth Hormone Released

Growth-hormone-releasing hormone (GHRH) acts on the GHRH receptor in the pituitary gland to alter the rate of GH gene transcription, increasing the amount of growth hormone produced and released [1]. GH secretion occurs immediately following a GHRH pulse, with the amount of GH released in response to an intravenous bolus dependent both on dose of GHRH and on how frequently the pituitary is stimulated with GHRH. Two main forms of GH account for most of the GH released in response to GHRH stimulation [2, 3], 22？K-hGH (191 amino acids) (approximately 75% of total secretion) and 20？K-hGH (176 amino acids) (5–10%) [4]. Numerous other forms are also detectable [5].The 20？K-hGH version lacks residues 32–46 as a result of alternate splicing within exon 3, but retains high biological activity on the GH receptor. It may bind less tightly to the extracellular domain of the GH receptor, but appears to have the same efficacy at the full length receptor [6]. The physiological importance of the different isoforms of GH in humans remains unclear as sensitive and specific immunoassays for 20？K-hGH have only been recently developed [7]. 22 and 20？K-hGH have almost identical somatogenic activity in prepubertal male and female dwarf rats [8], but this reflects interaction with rodent receptors which differ from human GH receptor.It is not known what controls the ratio of splicing of 20 versus 22？H-hGH products in the pituitary, and whether they are stored as efficiently, but when secretion is studied, the 22？K？:？20？K-hGH ratio remains constant when measured over a 24 hour period and following exercise [9]. In children the percentage of the 20？K-hGH isoform remains constant independent of age, sex, puberty, height, body mass index, and rate of GH production [10]. These observations have led to the suggestion that the overall production of 20？K-hGH is under the same regulation as that of 22？K-hGH. However, recent in vitro studies using transgenic mice pituitary cell lines have specifical