Growth hormone releasing factor induces prolactin secretion in acromegalic patients but not in normal subjects

Losa, Marco; Schopohl, Jochen; Müller, O. A.; Werder, Klaus von

doi:10.1530/acta.0.1090467

Cited by 35 publications

(10 citation statements)

References 15 publications

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“…Confirming our previous results (Losa et al , 1985a , it is conceivable that continuous GHRH infusion may be necessary to unmask this abnormal re¬ sponse in normal subjects. Addition of theophyl¬ line did not affect Prl-secretion.…”

Section: ) Ghrh Continuous Administration Cannotsupporting

confidence: 89%

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Theophylline blunts the GH-response to growth hormone releasing hormone in normal subjects

Losa

Huss

König

et al. 1986

Acta Endocrinologica

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Theophylline enhances GH-secretion in vitro, whereas in vivo a slight decrease of basal GH\x=req-\ levels has been observed. In the present study the effect of theophylline on the GH-responsiveness to acute and continuous administration of growth hormone releasing hormone (GHRH) was investigated. The following protocol was performed. 1) GHRH study. Fifty \ g=m\ g GHRH was given as an iv bolus followed by constant GHRH-infusion (100 \g=m\g/h) over 2 h after which another GHRH bolus of 50 \g=m\g was given.2) GHRH plus theophylline study. GHRH was administered as in the first study and theophylline was infused at a constant rate of 3.56 mg/min over 3 h, starting one h before the GHRH bolus.3) Theophylline study. Only saline and theophylline were infused. GHRH alone led to a GH-rise within 30 min with a maximum of 22.8 \m=+-\7.2 ng/ml (mean \m=+-\se) after which GH-levels decreased despite continuous GHRH-infusion to a nadir of 12.1 \m=+-\4.4 ng/ml at 105 min. The second GHRH bolus led to a minimal GH-increase (13.3 \m=+-\6.4 ng/ml at 135 min). Theophylline administration resulted in blunting of the GH-response to GHRH in all volunteers, with GH levels fluctuating between 4\p=n-\6 ng/ml throughout GHRH-administration. Theophylline alone did not affect GH-levels in three subjects studied, whereas in the other one a GH secretory episode 90 min after administration of the drug was observed. Prl showed a minimal increase only after the second GHRH bolus (from 254.2 \m=+-\7.7 \ g=m\ U/ ml to 317.3 \m=+-\96.0 \ g=m\ U/ ml in study 1, and from 139.3 \ m=+-\26.9 \ g=m\ U/ ml to 193.0 \ m=+-\32.6 \g=m\U/ml in study 2), TSH-levels did not change during any of the test-procedures and GHRH\x=req-\ levels were comparable in both study 1 and 2. Free fatty acids (FFA) rose progressively after theophylline administration (from 0.68 \m=+-\0.10 mEq/l to 1.06 \m=+-\0.08 mEq/l in study 2, and from 0.64 \m=+-\ 0.12 mEq/l to 1.09 \ m=+-\ 0.05 mEq/l in study 3), but also after GHRH alone (from 0.50 \m=+-\0.05 mEq/l to 0.78 \m=+-\0.11 mEq/l). This shows that therapeutical doses of theophylline blunt the GH-response to GHRH in normal subjects. The mechanisms involved may be a competition for the adenosine receptor at the pituitary, or an indirect effect mediated by the rise of FFA levels.

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Section: ) Ghrh Continuous Administration Cannotsupporting

confidence: 89%

“…GHRH has been shown to stimulate Prl-secretion in acromegalics (Losa et al 1985a) and in normal subjects if given in high dosages (Sassolas et al 1984). Furthermore, cAMP is involved in the control of Prl-secretion (Adams et al 1979).…”

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confidence: 99%

Theophylline blunts the GH-response to growth hormone releasing hormone in normal subjects

Losa

Huss

König

et al. 1986

Acta Endocrinologica

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“…Alternatively, the patients' raised prolactin levels may be the result of an acquired re sponse to GRF by the pituitary lactotrophs. Stimulation of prolactin secretion in many patients with acromegaly, and by mixed GH-PRL secreting human pituitary tumours in vitro, has been described [31][32][33], suggesting that non-specific responses to GRF may be related to pathological changes in the pitu itary.…”

Section: Discussionmentioning

confidence: 99%

Ectopic Corticotrophin-Releasing-Factor and Growth Hormone Releasing Factor Secretion: Diagnosis Using Human Pituitary Cell Culture

et al. 1987

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Cell culture of human pituitary tissue has been used to diagnose a patient with Cushing’s syndrome due to ectopic secretion of corticotrophin-releasing factor (CRF; case 1) and a case of acromegaly associated with ectopic secretion of a growth-hormone releasing factor (GRF; case 2). In both patients a pituitary tumour was not detected. Case 1 had a small cell carcinoma and symptoms of the ectopic ACTH syndrome, but in culture the carcinoma failed to secrete detectable ACTH. However, the culture medium used to maintain this carcinoma in vitro was found to contain a substance which stimulated ACTH secretion by human pituitary corticotrophs in cell culture. Radioimmunoassays and HPLC indicated that this substance had similar elution characteristics to human CRF and cross-reacted with antiserum to ovine CRF. Case 2 was found to have a lung tumour, the removal of which led to regression of her acromegalic symptoms. In culture, this tumour did not secrete GH, but did secrete a GRF. We conclude that the Cushing’s syndrome and acromegaly, in cases 1 and 2, respectively, were due to ectopic secretion of CRF and GRF leading to hyperstimulation of the pituitary gland.

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“…Taken together, the above-mentioned data indicate that the AP contains multi-functional (multi-responsive and/or polyhormonal) cells, whose stimulation may give rise to so-called paradoxical secretion. Paradoxical secretory responses are common in non-normal pituitaries, especially in pituitary tumours [3,11,23,25,32], but they have been also sporadically reported in normal pituitaries, both in vitro and in vivo, including healthy humans [2,12,16].…”

Section: Introductionmentioning

confidence: 99%

Phenotypic characterization of multi-functional somatotropes, mammotropes and gonadotropes of the mouse anterior pituitary

Alonso

Núñez

García‐Sancho

2004

Pflugers Arch - Eur J Physiol

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The existence of bihormonal anterior pituitary (AP) cells co-storing growth hormone and either prolactin (mammosomatotrope) or gonadotropins (somatogonadotrope) has been described. These cells have been proposed to be involved in "paradoxical" secretion [secretion of an AP hormone induced by a non-related hypothalamic releasing factor (HRH) and transdifferentiation (a phenotypic switch between different cell types without cell division]. Here we combine calcium imaging (to assess HRH responsiveness) and multiple sequential immunoassay of the six AP hormones to perform a single-cell phenotypic study of multifunctional somatotropes, mammotropes and gonadotropes in the normal male and female mouse pituitaries. AP cell phenotypes differed from the classic view, showing multiple HRH-receptor expression and/or hormone storage. Mammosomatotropes represented only 5-6% of somatotropes and were poorly responsive to HRHs, suggesting that their contribution to paradoxical secretion should be very limited. Somatogonadotropes were present only in females and contained adrenocorticotropic hormone. They responded to growth hormone-releasing hormone but failed to respond to gonadotropin-releasing hormone (LHRH). Other polyhormonal cells identified include (1) gonadocorticotropes, restricted to females, where they make up more than 50% of all the gonadotropes and contain other AP hormones; (2) gonadomammotropes, which are present preferentially in female cells and respond to LHRH; and (3) gonadothyrotropes, which are present similarly in male and female pituitaries.

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Growth hormone releasing factor induces prolactin secretion in acromegalic patients but not in normal subjects

Cited by 35 publications

References 15 publications

Theophylline blunts the GH-response to growth hormone releasing hormone in normal subjects

Theophylline blunts the GH-response to growth hormone releasing hormone in normal subjects

Ectopic Corticotrophin-Releasing-Factor and Growth Hormone Releasing Factor Secretion: Diagnosis Using Human Pituitary Cell Culture

Phenotypic characterization of multi-functional somatotropes, mammotropes and gonadotropes of the mouse anterior pituitary

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