Studies on the Conditions Determining the Inhibitory Effect of Somatostatin on Adrenocorticotropin, Prolactin and Thyrotropin Release by Cultured Rat Pituitary Cells

Abstract

Somatostatin (SRIH) is a physiological inhibitor of growth hormone (GH) secretion, but its role in the regulation of adrenocorticotropic hormone (ACTH), prolactin (PRL) and thyroid-stimulating hormone (TSH) release is unclear. SRIH (1 pM to 1 µM) did not affect basal and corticotropin-releasing hormone (CRH)-stimulated ACTH release by normal rat pituitary cells cultured in medium with 10% fetal calf serum (FCS). In cells deprived of serum for 48 h, or preincubated with the glucocorticoid-receptor-blocking agent, RU 38486, CRH-stimulated ACTH release was significantly suppressed by 1 pM to 0.10 nM SRIH. Preincubation with 5 nM dexamethasone completely abolished this inhibitory effect of SRIH on ACTH release. PRL release by pituitary cells cultured in phenol red-free culture medium with 10% estrogen-stripped FCS showed a very low sensitivity to SRIH. Increasing concentrations of 10 and 50 pM and 1 nM estradiol made PRL release by these cells significantly less sensitive to 50 nM dopamine, whereas the sensitivity to SRIH increased to a similar extent. In all instances dopamine and SRIH together exerted additive inhibitory effects, the extent of which remained similar under all conditions. After a 2-hour incubation, thyrotropin-releasing hormone-stimulated TSH secretion was significantly suppressed by 100 nM and 1 µM SRIH only in cells cultured in medium with 10% hypothyroid serum, and not in cells cultured in medium with 10% FCS. Such a difference in the sensitivity of thyrotrophs to SRIH disappeared during longer incubation. Conclusions: (1) ACTH release by normal corticotrophs is only sensitive to SRIH in the absence of the physiological peripheral feedback regulation by glucocorticoids. (2) PRL release by normal lactotrophs is sensitive to SRIH in the presence of physiological concentrations of estradiol. As the estradiol concentration increases, the dopamine sensitivity of PRL release decreases to the same extent as SRIH sensitivity increases, while the additive inhibitory effect of the combination of dopamine and SRIH remains the same. (3) TSH release by normal thyrotrophs is more sensitive to SRIH if the cells have been cultured in hypothyroid serum. (4) The reaction of corticotrophs, lactotrophs and thyrotrophs to SRIH seems to be determined by the concentration of the respective ‘peripheral’ physiological feedback hormones.

Review: Central non-glucocorticoid inhibitors of the hypothalamo-pituitary-adrenal axis

“…There is more convincing evidence for the effects of SRIF in rats: it inhibited CRH-stimulated ACTH release from isolated pituitary cells (Lamberts et al 1989) and inhibited CRH release from hypothalami in vitro (Tizabi & Calogero 1992). Thus SRIF is effective at both the hypothalamic and anterior pituitary levels in rodents, but the absence of evidence for an effect of SRIF in normal human subjects suggests that this peptide plays little part in regulating the human HPA axis.…”

Somatostatin and somatostatin receptors in Cushing's disease

“…On the other hand, SS inhibited CRH-and vasopressin induced ACTH release by cultured cells prepared from long-term adrenalectomized rats [29]. Moreover, in serum-deprivedor in rat pituitary cells pre-treated with the glucocorticoid blocking agent RU-38146, SS inhibited CRH-induced ACTH secretion already at low nanomolar concentrations, whereas in serum cultured cells SS was unable to influence ACTH secretion [30]. In humans, systemic SS infusion did not suppress basal-or angiotensin II-, ghrelin-or CRH-induced ACTH or cortisol concentrations [31][32][33].…”

Thyroid-Stimulating Hormone Regulation and Transcription in Hypothyroidism

“…Somatostatin suppresses TSH secretion from the pituitary gland (Lamberts et al, 1989), and its analogues are therefore used for the treatment of TSH-producing adenomas (Beck-Peccoz et al, 1989).…”