Abnormal growth hormone responses to CB-154 and thyrotropin-releasing hormone (TRH) in patients with acromegaly.

Factors determining the effectiveness of CB-154 in the treatment of acromegaly.

“…Moreover, we indicated that the treatment is not always effective in a more responsive type; namely this therapy was effective only in cases which were more responsive to TRH and less responsive to arginine. This is well correlated to our previous findings that GH decreases induced by acute administration of CB-154 are much greater in TRH responsive and arginine non-responsive patients (Hanew et al 1979).…”

“…However, one possibility might be that CB-154 has dual actions; i.e. (1) direct suppressive effect of GII cells acting on the sites related to TRH actions, as Liuzzi et al (1974) indicated the mutual relationship between abnormal GH responses to TRH and to dopaminergic agonists, and (2) indirect stimulatory effect on the cells acting on the sites related to GH-RF (GH-releasing factor) where arginine might act (Martin 1973; Merimee and Rabin 1973; Hanew et al 1979). Based on these phenomena, GH levels might be lowered when the direct GII suppressive effect of CB-154 is more dominant than the indirect stimulatory effect and vice versa.…”

“…However, it is not clear whether all of more responsive patients do really respond to the treatment. Previously we have reported that CB-154-induced GH decreases are greater in cases which are more responsive to TRH and less responsive to arginine (Hanew et al 1979). In this study we examined the relationship between GH changes induced by chronic CB-154 treatment and GH responses to acute TRH or arginine administration before the treatment.…”

Single-Cell Phenotypic Characterization of Human Pituitary GHomas and Non-Functioning Adenomas Based on Hormone Content and Calcium Responses to Hypothalamic Releasing Hormones

“…Other GHomas stored only GH but responded to all four HRH (type II GHomas) or were polyhormonal cells lacking responses to any HRH (type I GHomas). The presence of multifunctional cells (multiresponsive and/or polyhormonal cells) in human GHomas may explain, in a simple way, the occurrence of paradoxical secretion, which has been frequently reported in pituitary tumors ( 6 – 13 ). Consistently, the most common phenotype of GHomas made of polyhormonal GH cells and showing responses to both TRH and GHRH may explain paradoxical secretion of GH induced by several HRHs, most notably TRH.…”

“…According to the monoclonal hypothesis, cells from GH-secreting tumors should express functional receptors for GH-releasing hormone (GHRH) and store and release GH. However, paradoxical secretion of alternative anterior pituitary (AP) hormones has been reported in multiple instances of pituitary adenoma, including GHoma patients responding to thyrotropin-releasing hormone (TRH) with GH secretion ( 6 – 9 ) and acromegaly patients producing prolactin (PRL) upon GHRH administration ( 10 ). Paradoxical secretion has been also noticed in normal pituitary glands, both in vitro and in vivo ( 11 , 12 ).…”