ABSTRACT
Somatostatin (SRIF), a hypothalamic inhibitor of pituitary growth hormone (GH) and thyroid-stimulating hormone (TSH) secretion, binds to five distinct receptor (SSTR) subtypes. We therefore tested SSTR subtype-specific SRIF analogs in primary human fetal pituitary cultures (23-25-wk gestation) to elucidate their role in regulating human pituitary function. Using reverse transcription-PCR, mRNA expression of SSTR2 and SSTR5 were detected in fetal pituitary by 25 wk. SRIF analog affinities were determined by membrane radioligand binding in cells stably expressing the human SSTR forms. GH secretion was suppressed equally (40-60%, P < 0.005) by analogs preferential for either SSTR2 (IC50 for receptor binding affinity, 0.19-0.42 nM) or SSTR5 (IC50, 0.37 nM), and compounds with enhanced affinity for SSTR2 were more potent (EC50 for GH suppression, 0.05-0.09 nM) than Lanreotide (EC50, 2.30 nM) and SRIF (EC50, 0.19 nM). Similarly, analogs with high affinity for SSTR2 or SSTR5 decreased TSH secretion (30-40%, P < 0.005). However, prolactin was effectively inhibited only by compounds preferentially bound to SSTR2 (20-30%, P < 0.05). Luteinizing hormone was modestly decreased (15-20%) by SSTR2- or SSTR5-specific analogs. An SSTR5-specific analog also exclusively inhibited GH in acromegalic tumor cells. Thus, SRIF regulation of GH and TSH in primary human fetal pituitary cells is mediated by both SSTR2 and SSTR5, both of which are abundantly expressed by 25 wk. In contrast, suppression of prolactin is mediated mainly by SSTR2. These results indicate that SSTR5 is critical for physiologic regulation of GH and TSH. SRIF analogs with selective affinity for this receptor may therefore be more effective in the treatment of hormone-secreting pituitary adenomas.
Subject(s)
Human Growth Hormone/metabolism , Pituitary Gland/metabolism , Prolactin/metabolism , Receptors, Somatostatin/physiology , Thyrotropin/metabolism , Adrenocorticotropic Hormone/drug effects , Binding Sites , Cells, Cultured , Female , Fetus , Growth Hormone/analogs & derivatives , Growth Hormone/drug effects , Growth Hormone/pharmacology , Human Growth Hormone/drug effects , Humans , Luteinizing Hormone/drug effects , Male , Pituitary Gland/cytology , Prolactin/drug effects , RNA, Messenger/biosynthesis , Receptors, Somatostatin/classification , Receptors, Somatostatin/genetics , Thyrotropin/drug effectsSubject(s)
HIV Infections/metabolism , HIV-1/physiology , Interleukin-1/biosynthesis , Interleukin-6/biosynthesis , Microglia/metabolism , beta-Endorphin/pharmacology , Cells, Cultured , Female , Fetus/metabolism , Fetus/virology , Humans , Microglia/virology , Pregnancy , Receptors, Opioid/agonists , Receptors, Opioid/metabolism , Virus Replication/drug effectsABSTRACT
A catheter-based, miniature ultrasound transducer, operating at a frequency of 12.5 MHz, was introduced transcervically into the uterine cavity of 18 pregnant women about to undergo first-trimester abortion. Transcervical sonography showed the yolk sac and embryonic structures, such as brain vesicles, limb buds, liver, spinal canal, and umbilical cord with blood flow, in eight embryos at 5-8 menstrual weeks of age. As an investigational technique, catheter-assisted transcervical sonography offers a new diagnostic approach to imaging of the first-trimester human embryo.
