Growth hormone secretion elicited by GHRH, GHRP‐6 or GHRH plus GHRP‐6 in patients with microprolactinoma and macroprolactinoma before and after bromocriptine therapy

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Abstract
Growth hormone-releasing peptides (GHRPs) are potent GH releasers which act at both pituitary and hypothalamic levels through specific G-protein coupled receptors, recently cloned. A synergistic effect from the simultaneous administration of GHRH + GHRP-6 on GH release is observed in normal subjects, while it is absent in patients with hypothalamo-pituitary disconnection. We studied the effects of GHRH, GHRP-6 and both secretagogues on GH release in patients harbouring pituitary tumours that may be reduced in size by medical treatment. Analysis of peak GH response to GHRH, GHRP-6 and GHRH plus GHRP-6 in patients with micro- and macroprolactinomas. Integrated GH response over 2 hours calculated as AUG-GH mU/l x 120 min. Analysis of delta PRL above the basal level in response to the same GH releasers. Eleven patients with macroprolactinomas aged 41.2 +/- 4.8 years (range 24-75), nine patients with microprolactinomas aged 31.5 +/- 3.4 (range 22-53) and 13 healthy subjects aged 42.1 +/- 4.7 years (range 22-64) were studied. Prolactinoma patients were then treated with bromocriptine (15-20 mg orally) for 6-24 months. Tests were repeated when there was evidence of tumour shrinkage and normalized plasma prolactin concentrations. Peak GH response before treatment in macroprolactinoma patients was 4.9 +/- 0.9 mu/l after GHRH, 8 +/- 4 mU/l after GHRP-6 and 18 +/- 5 mU/l after GHRH + GHRP-6. Synergism was absent. AUC were 390 +/- 90; 500 +/- 100 and 1100 +/- 300 mU/l x 120 min respectively. These values were all significantly different (P < 0.05) from normal subjects and patients with microprolactinomas with peak GH 16.8 +/- 0.9 mU/l after GHRH; 43 +/- 6 mU/l after GHRP-6 and 130 +/- 10 mU/l after GHRH + GHRP-6. AUC-GH was 1200 +/- 400 after GHRH, 2200 +/- 400 after GHRP-6 and 9000 +/- 1000 mU/l x 120 min after GHRH + GHRP-6. As in normal subjects, synergism was preserved in patients with microprolactinoma (P > 0.05). After treatment with bromocriptine peak GH in patients with macroprolactinoma was 8 +/- 4 mU/l after GHRH, 22 +/- 5 mU/l after GHRP-6 and 70 +/- 20 mU/l after GHRH + GHRP-6. AUC-GH was 800 +/- 300, 1100 +/- 300 and 3500 +/- 800 mU/l x 120 min, respectively. The response of GH after GHRP-6 and GHRH + GHRP-6 improved significantly (P < 0.05) in treated patients with macroprolactinoma. There was no significant change in GH response in microprolactinoma patients after treatment with bromocriptine. Peak GH after GHRH was 30 +/- 20 mU/l, after GHRP-6 it was 75 +/- 8 mU/l and after GHRH + GHRP-6 it was 200 +/- 30 mU/l. AUC-GH was 1500 +/- 700 after GHRH, 4500 +/- 500 after GHRP-6 and 15,100 +/- 600 mU/l x 120 min. Delta prolactin after GHRP-6 did not change before and after bromocriptine treatment in patients with macroprolactinoma or microprolactinoma. GH release after GHRP-6 or GHRH + GHRP-6 is fully preserved in patients with microprolactinomas and does not differ before and after treatment with bromocriptine. Patients with macroprolactinoma have blunted responses of GH after GHRH and GHRP-6 and synergism is severely compromised. GH responsiveness to and synergistic interaction between GHRH and GHRP-6 recovers after shrinkage of macroprolactinoma with bromocriptine. Prolactin release stimulated by intravenous administration of GHRP-6 in healthy subjects was not seen in patients with micro- or macroprolactinomas.

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