Inhibitory effects of somatostatin analogs on prolactin secretion in rats pretreated with estrogen or haloperidol

T. Karashima, Andrew V Schally

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9 Citations (Scopus)

Abstract

The effect on prolactin (PRL) secretion of acute administration of new octapeptide analogs of somatostatin (SS) with an enhanced and prolonged growth hormone inhibitory activity was investigated in rats under various pretreatment conditions with estrogen and antidopaminergic drugs. Analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121), at a dose of 5 μg/100 g body wt, did not decrease basal PRL levels in thiopental-anesthetized female rats, untreated or treated with estrogen benzoate (EB) (8 μg/rat) for 5 days. When haloperidol was used to elevate PRL level, a single injection of RC-121 inhibited PRL release in EB-pretreated female rats or untreated female and male rats. Analog D-Phe-Cys-Trp-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160), which has a potency similar to RC-121 in the tests on inhibition of GH, in a dose of 0.2 μg/100 g body wt, did not lower the elevated PRL level induced by α-methyl-p-tyrosine and/or pretreatment with EB (100 μg/rat, 3 and 6 days before) in pentobarbital-anesthetized male rats. However, both analogs RC-121 and RC-160, in doses of 0.2 μg/100 g body wt, decreased the PRL levels elevated by prolonged treatment with EB (100 μg/rat, twice a week for 3 weeks) in male rats. These results indicate that acute administration of these SS analogs can induce a prolonged inhibition of PRL release when PRL is acutely elevated by haloperidol or chronically elevated by 3 weeks of estrogen administration. Future additional studies are required to investigate the effects of chronic administration of these SS analogs on PRL levels.

Original languageEnglish
Pages (from-to)69-75
Number of pages7
JournalProceedings of the Society for Experimental Biology and Medicine
Volume185
Issue number1
StatePublished - Jan 1 1987
Externally publishedYes

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Haloperidol
Somatostatin
Prolactin
Rats
Estrogens
Benzoates
Thiopental
Pentobarbital
Growth Hormone
Tyrosine
Injections
RC 121

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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title = "Inhibitory effects of somatostatin analogs on prolactin secretion in rats pretreated with estrogen or haloperidol",
abstract = "The effect on prolactin (PRL) secretion of acute administration of new octapeptide analogs of somatostatin (SS) with an enhanced and prolonged growth hormone inhibitory activity was investigated in rats under various pretreatment conditions with estrogen and antidopaminergic drugs. Analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121), at a dose of 5 μg/100 g body wt, did not decrease basal PRL levels in thiopental-anesthetized female rats, untreated or treated with estrogen benzoate (EB) (8 μg/rat) for 5 days. When haloperidol was used to elevate PRL level, a single injection of RC-121 inhibited PRL release in EB-pretreated female rats or untreated female and male rats. Analog D-Phe-Cys-Trp-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160), which has a potency similar to RC-121 in the tests on inhibition of GH, in a dose of 0.2 μg/100 g body wt, did not lower the elevated PRL level induced by α-methyl-p-tyrosine and/or pretreatment with EB (100 μg/rat, 3 and 6 days before) in pentobarbital-anesthetized male rats. However, both analogs RC-121 and RC-160, in doses of 0.2 μg/100 g body wt, decreased the PRL levels elevated by prolonged treatment with EB (100 μg/rat, twice a week for 3 weeks) in male rats. These results indicate that acute administration of these SS analogs can induce a prolonged inhibition of PRL release when PRL is acutely elevated by haloperidol or chronically elevated by 3 weeks of estrogen administration. Future additional studies are required to investigate the effects of chronic administration of these SS analogs on PRL levels.",
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N2 - The effect on prolactin (PRL) secretion of acute administration of new octapeptide analogs of somatostatin (SS) with an enhanced and prolonged growth hormone inhibitory activity was investigated in rats under various pretreatment conditions with estrogen and antidopaminergic drugs. Analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121), at a dose of 5 μg/100 g body wt, did not decrease basal PRL levels in thiopental-anesthetized female rats, untreated or treated with estrogen benzoate (EB) (8 μg/rat) for 5 days. When haloperidol was used to elevate PRL level, a single injection of RC-121 inhibited PRL release in EB-pretreated female rats or untreated female and male rats. Analog D-Phe-Cys-Trp-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160), which has a potency similar to RC-121 in the tests on inhibition of GH, in a dose of 0.2 μg/100 g body wt, did not lower the elevated PRL level induced by α-methyl-p-tyrosine and/or pretreatment with EB (100 μg/rat, 3 and 6 days before) in pentobarbital-anesthetized male rats. However, both analogs RC-121 and RC-160, in doses of 0.2 μg/100 g body wt, decreased the PRL levels elevated by prolonged treatment with EB (100 μg/rat, twice a week for 3 weeks) in male rats. These results indicate that acute administration of these SS analogs can induce a prolonged inhibition of PRL release when PRL is acutely elevated by haloperidol or chronically elevated by 3 weeks of estrogen administration. Future additional studies are required to investigate the effects of chronic administration of these SS analogs on PRL levels.

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