垂体生长激素分泌瘤细胞有关生长抑素调节的受体和受体后…

为了解生长抑素在人垂体生长激素分泌瘤发病中的作用，在２５例肢端肥大症患者体外培养的垂体瘤细胞观察了ＳＲＩＦ激动剂，抑制性鸟苷酸调节蛋白拮抗剂百日咳毒素和钙离子载体Ａ２３１８７对ＧＨ分泌的影响，以及ＳＭＳ对细胞内ｃＡＭＰ水平的抑制作用。     

睾丸女性化综合征患者外阴部皮肤成纤维细胞雄激素受体的研究

以培养的外阴部皮肤成纤维细胞（ＧＳＦ）为材料，以人工合成的雄激素（￣３Ｈ－Ｒ１８８１）为配体，采用完整细胞及核特异结合以及受体热稳定性的测定方法，对６例完全型及不完全型睾丸女性化（ＴＦＭ）综合征患者ＧＳＦ的雄激素受体（ＡＲ）进行了研究，实验显示，６个患者中有３个ＧＳＦ系与￣３Ｈ－Ｒ１８８１的特异结合量明显减少，１个患者ＧＳＦ系的核与￣３Ｈ－Ｒ１８８１的特异结合量降低，另外两患者ＧＳＦ系的所测指标没发现有明显异常。上述结果表明ＡＲ质或量的异常是导致ＴＦＭ综合征的主要原因。     

粘附分子对CD3介导的胸腺细胞[Ca^2＋]i应答的影响

ＬＦＡ－１和ＩＣＡＭ－１广泛表达于各胸腺细胞亚群，但ＩＣＡＭ－１在ＰＮＡ￣＋细胞的表达下调。本文报道：用抗ＬＦＡ－１／ＩＣＡＭ－１和抗ＣＤ３单抗，分析了粘附分子ＬＦＡ－１／ＩＣＡＭ－１对抗ＣＤ３诱导的胸腺细胞［Ｃａ￣（２＋）］ｉ应答的影响。结果显示，可溶性抗ＬＦＡ－１／ＩＣＡＭ－１可抑制ＣｏｎＡ刺激的胸腺细胞增殖，且以抗ＬＦＡ－１抗体的作用更为显著，在ＣｏｎＡ或抗ＣＤ３诱导的胸腺细胞［Ｃａ￣（２＋）］ｉ应答中，抗ＬＦＡ－１单抗可明显抑制［Ｃａ￣（２＋）ｉ升高。但如果用二抗交联ＣＤ３和ＬＦＡ－１，胸腺细胞［Ｃａ￣（２＋）ｉ则显著高于单独交联ＣＤ３时的水平（Ｐ＜０．０１），而ＣＤ３与ＩＣＡＭ－ｌ交联却无此效应，此外，仅交联ＬＦＡ－１或ＩＣＡＭ－１也无诱导［Ｃａ￣（２＋）］ｉ应答的作用。提示在ＬＦＡ－ｌ与ＩＣＡＭ－１介导的胸腺细胞与胸腺基质细胞相互作用中，ＬＦＡ－１可为ＴＣＲ／ＣＤ３途径介导的胸腺细胞活化提供复合刺激信号。     

rhIL－2调节离体boPBMC增殖和分泌Ig的作用

应用￣３Ｈ－ＴｄＲ掺入法、ＥＬＩＳＡ和ＦＡＣＳ研究了ｒＨＩＬ－２调节离体奶牛外周血单核细胞（ｂｏＰＢＭＣ）免疫应答的特点。ｒｈＩＬ－２能诱导细胞持续性增殖和分泌Ｉｇ，尤其是分泌ＩｇＡ和ＩｇＧ＿２（与ＰＷＭ相比，Ｐ＜０．０１）；还能增强ＰＷＭ诱导的Ｉｇ分泌，但不改变ＳＥＢ抑制Ｉｇ分泌的作用。细胞表型也表明，ｒｈＩＬ－２对ＰＷＭ或ＳＥＢ诱导的ｂｏＰＢＭＣ中ＣＤ４￣＋或ＣＤ８￣＋细胞增殖作用无选择性。     

OF抑制试验对A族β溶血性链球菌的分型

本研究通过ＯＦ（ＯｐａｃｔｏＦａｃｔｏｒ，混度因子）抑制试验对临床分离的１１０株Ａ族β溶血性链球菌（ＧＡβＨＳ）进行ＯＦ分型。结果表明，（１）ＯＦ分型阳性率仅有３０％。（２）ＯＦ阳性菌株集中在Ｍ６８，Ｍ７５，Ｍ６０，ＰＴ２８４１，Ｍ２２五个Ｍ型，其中Ｍ６８，Ｍ７５明显占优势达６６．６％。（３）全部Ｍ６８型菌株均取自咽扁桃体炎和猩红热患儿，大部分脓疮病ＯＦ阳性株为Ｍ７５株。提示：（１）我国儿童ＧＡ６ＨＳ感染流行菌株有明显不同于欧美等国家的Ｍ／ＯＦ菌型谱。（２）这时期在北京地区有Ｍ６８，Ｍ７５感染菌株的局部流行。（３）对我国ＧＡＲＨＳ感染菌株分型研究应在采用Ｍ／ＯＦ方法的基础上，进一步探讨其它分型方法。     

肝刺激因子对大鼠肝细胞EGF受体基因表达调控的初步研究

以超速离心法制备大鼠肝刺激因子（ＨＳＳ）。彩和无血清培养技术培养大鼠肝细胞并观察ＨＳＳ作用肝细胞后不同时刻肝细胞ＥＧＦ受体ｍＲＮＡ表达的变化。结果显示，ＨＳＳ可刺激ＥＧＦ受体ＭＲＮＡ的表达，给药后２－６ｈ，ｍＲＮＡ表达高峰，ＨＳＳ与ＥＧＦ合用可明显刺激受体ｍＲＮＡ表达。Ｎｏｒｔｈｅｒｎ杂交分析表明，ｍＲＮＡ表达明显增高系由于５．６和１０．０ｋｂ两基因片段所致，提示ＨＳＳ可在基因水平调节ＥＧＦ受体活     

大鼠免疫细胞的促肾上腺皮质激素受体的研究

大鼠免疫细胞都有高、低亲和力两类ＡＣＴＨ受体。脾脏细胞高亲和力促肾上腺皮质激素（ＡＣＴＨ）受体的解离常数（ＫＤ）为０．１１ｎｍｏｌ／Ｌ，最大结合量（Ｂｍａｘ）为１．２ｆｍｏｌ／２×１０￣６细胞，３６６位点／细胞，低亲和力受体ＫＤ为５．７ｎｍｏｌ／Ｌ，Ｂｍａｘ为１４７ｆｍｏｌ／２×１０￣６细胞，４２０００位点／细胞。外周血淋巴细胞（ＰＢＬ）高亲和力ＡＣＴＨ受体的ＫＤ值为０．１５ｎｍｏｌ／Ｌ，Ｂｍａｘ为１．２ｆｍｏｌ／１×１０￣６细胞，１５８０位点／细胞，低亲和力受体ＫＤ值为６．１ｎｍｏｌ／Ｌ，Ｂｍａｘ为３７．５ｆｍｏｌ／１×１０￣６细胞，３２０００位点／细胞。胸腺细胞、Ｔ、Ｂ淋巴细胞及腹腔巨噬细胞（Ｍφ）亦具有高、低亲和力不同的ＡＣＴＨ受体。     

乙酰胆碱对大鼠腹腔巨噬细胞内钙离子浓度和表面Ia抗原表达的影响

用Ｆｕｒａ－２作为荧光探针测定大鼠腹腔巨噬细胞（Ｍ）内钙离子浓度（［Ｃａ￣（２＋）］ｉ），ＡＰＡＡＰ桥联酶标法检测Ｍ表面Ｉａ抗原的表达。结果表明：５×１０￣（－６）ｍｏｌ／Ｌ的乙酞胆碱（Ａｃｈ）可使Ｍ［Ｃａ￣（２＋）］ｉ；明显上升，可促进Ｍ表面Ｉ－Ａ和Ｉ－Ｅ抗原的表达，而阿托品（１０￣（－５）ｍｏｌ／Ｌ）可阻断Ａｃｈ升高［Ｃａ￣（２＋）］ｉ的作用。阿托品、三氟啦嚎（ＴＦＰ，５０μｍｏｌ／Ｌ）、ＥＧＴＡ（６ｍｍｏｌ／Ｌ）均可阻断Ｍ促进ＭＩａ抗原表达的作用，ｃＡＭＰ依赖性蛋白激酶抑制剂（ＰＫＩ，２５μｇ／ｍｌ）对Ａｃｈ促进ＭＩａ抗原表达的作用无影响。     

促性腺激素释放激素 GnRH 相关肽存在于培养的大鼠垂体前叶促性腺激素细胞

为了探讨垂体促性腺激素细胞中ＧｎＲＨ相关肽（ＧＡＰ）的来源，本实验选用两种特异性抗ＧＡＰ抗体和抗ＦＳＨ－β抗体，采用免疫细胞化学双重染色技术，研究了ＧＡＰ在培养的大鼠垂体前叶细胞内的分布和定位。结果发现一些培养细胞可表达ＧＡＰ，而且ＧＡＰ免疫反应产物和ＦＳＨ免疫反应产物共存于同一种细胞。这表明ＧＡＰ存在于培养的大鼠垂体前叶促性腺激素细胞内。本文讨论了ＧＡＰ的来源及其可能的生物学作用。     

促性腺激素释放激素GnRH相关肽存在于培养的大鼠垂体前叶促性腺激素…

为了探讨垂体促性腺激素细胞中ＧｎＲＨ相关肽（ＧＡＰ）的来源，本实验选用两种特异性抗ＧＡＰ抗体和抗ＦＳＨ－β抗体，采用免疫细胞化学双重染色技术，研究了ＧＡＰ在培养的大鼠垂体前叶细胞内的分布和定位。结果发现一些培养细胞可表达ＧＡＰ，而且ＧＡＰ免疫反应产物和ＦＳＨ免疫反应产物共存于同一种细胞。这表明ＧＡＰ存在于培养的大鼠垂体前叶促性腺激素细胞内，本文讨论了ＧＡＰ的来源及其可能的生物学作用。     

Somatostatin inhibits prolactin secretion by multiple mechanisms involving a site of action distal to increased cyclic adenosine 3',5'-monophosphate and elevated cytosolic Ca2+ in rat lactotrophs

The release of prolactin (PRL) from a clonal cell-line of anterior pituitary cells (GH4C1) was inhibited by somatostatin (SRIH) in a dose-dependent manner (ED50 nM). The inhibition (20% of control levels) was detectable within 50 s and maximal within 90 s. Thyroliberin (TRH) enhancement of PRL secretion was biphasic. SRIH inhibited both phases equally. Ionomycin in combination with the phorbol ester, TPA, mimics the TRH-elicited PRL release, and SRIH partly inhibited this effect. SRIH had no effect on TRH-stimulated formation of inositol trisphosphate, and only small effects on TRH-activated adenylate cyclase. Vasoactive intestinal peptide (VIP) and forskolin stimulated cAMP formation and PRL release potently. SRIH inhibited both effects of VIP and forskolin, and there was a close correlation between the inhibition of PRL secretion and cAMP accumulation. 8-Bromo-cAMP enhanced PRL release, an effect that was also partly reduced by SRIH. The Ca2+ channel activator, BAY-K-8644 and high extracellular K+ increased PRL release, and SRIH caused a partial reduction in the release response to both secretagogues. SRIH lowered [Ca2+]i, and markedly reduced the rise in [Ca2+]i elicited by TRH, VIP and K+. SRIH did not influence the Ca2+ spikes recorded in Na+-free solution, and had no effect on the TRH-induced membrane potential changes. Our results demonstrate that SRIH may inhibit PRL release from GH4C1 cells by (1) inhibiting hormone-sensitive adenylate cyclase, (2) blocking the effect of cAMP and (3) lowering [Ca2+]i. None of these effects is, however, sufficient to explain all the effects of SRIH, suggesting that SRIH also exerts a major action at a step subsequent to cAMP accumulation and [Ca2+]i elevation. Since the GH4C1 cells possess one single class of binding sites, this implies that the same SRIH receptor is coupled to several cellular signalling systems.     

The time course and extracellular Ca2+ involvement of growth hormone (GH) releasing factor-induced GH secretion in perifused dispersed rat pituitary cells

The time course of GH secretion in response to hpGRF and its dependency on the extracellular Ca2+ concentration were studied in perifused dispersed anterior pituitary cells. The onset of GH secretion in response to 1 nM hpGRF was relatively rapid (within 5 s) but removal of hpGRF after 10-min application further increased the rate of secretion (off-response). The threshold and maximum concentrations of hpGRF in stimulatory secretion were 10(-12) and 10(-8) M respectively. Between these two concentrations, the responses showed dose dependency. A reduction in the extracellular Ca2+ concentration to 0.25 mM or to nominally zero reduced hpGRF-induced GH secretion to 64.4% or to 1.9%, respectively, of the control response in the presence of 2.5 mM Ca2+. Two mM Co2+, known as a strong calcium channel blocker, completely suppressed hpGRF-induced GH secretion. The removal of Ca2+ from the perifusion buffer immediately after the offset of 1 min-applied 1 nM hpGRF accelerated the falling phase of GH secretion, which is parallel to the decline in [Ca2+]o in the perifusion chamber. Under nominal Ca2+-free conditions, hpGRF produced no increase in GH secretion. However, 10 min after the offset of 1 min-applied hpGRF under Ca2+-free conditions, the introduction of normal buffer containing 2.5 mM Ca2+ substantially restored GH secretion, although after 20 min the introduction of normal buffer produced only a slight increase in GH secretion. In perifusion experiment of 10(6) cells, intracellular cyclic AMP (cAMP) content was raised from the basal value of 4 to 26 pmol by 2-min application of 1 nM hpGRF. After cessation of hpGRF application, cAMP content decreased to 8.7 pmol at 11 min and returned to the basal value by 20 min. The same tendency was observed in Ca2+-free buffer. In conclusion, the extracellular Ca2+ was essential for hpGRF-induced GH secretion. This indicates the importance of the influx of Ca2+ in response to hpGRF. The time course of hpGRF-induced rise and fall in cAMP content was roughly parallel to the GH secretion. The possible explanations of the off-response and the restoration of GH secretion by reintroducing normal buffer were discussed.     

“交叉通讯”在人垂体生长激素腺瘤激素分泌中的调控作用研究

目的:探讨在人垂体生长激素腺瘤中,细胞内信号的交叉通讯对生长激素分泌的调控作用。方法:采用体外垂体生长激素(GH)腺瘤细胞培养方法,观察在生长激素释放激素(GHRH)和人工合成的GH释放肽(GHRP-6)刺激下,2种垂体腺瘤细胞内信号系统的交叉通讯在GH释放中的调控作用。结果:GHRH和GHRP-6对垂体腺瘤的GH分泌有协同刺激效应。cAMP、PKC在两种信号传导系统的交叉通讯中起着重要作用。结论:在垂体GH腺瘤的激素释放调控中,多种细胞内信号的“交叉通讯”有重要意义。     

Wirkungen von Strahlentherapie und inhibierenden Medikamenten auf die Hypophyse und ihre Adenome

Radiation therapies of pituitary adenomas induce an increase in fibroses and nuclear pleomorphism. Most growth hormone (GH) secreting pituitary adenomas react to somatostatin analogues by a distinct decrease of GH secretion. In two thirds, levels of IGF-1 can be normalized. Some cases show a shrinkage of adenomas that correlates with fibrosis of the tumor. With these drugs, thyroid stimulating hormone secreting adenomas can also be treated. Prolactin secreting adenomas are mostly treated primarily with dopamine agonists. Up to 90% of cases show a strong decrease in hormone secretion and a distinct shrinkage of the adenomas based on strong decrease in adenoma cell volume. Long-term medication with high doses of glucocorticoids induces Crooke's cells in the anterior pituitary. These are suppressed ACTH cells and characterized by increased numbers of large lysosomes and dense bundles of cytofilaments.     

Neurohormones coming from the normal and tumoral human anterior pituitary. Secretion and regulation in vitro

Several neuropeptides, classically associated with the hypothalamus have been found in the anterior pituitary and their local synthesis has been hypothesized. Using normal and tumoral human pituitaries we found in the tissue itself different neuropeptides (TRH, SRIH, GHRH) and dopamine in variable quantities according to the nature of the tissue. They were all present in normal pituitaries while only stimulatory neurohormones like TRH and GHRH were found in tumoral tissue implying an imbalance between the stimulatory and inhibitory control of hypophyseal hormones (PRL and GH) in pituitary adenomas. Fragments from normal pituitaries and dispersed cells from GH, PRL and nonsecreting adenomas, were perifused for 4 hours in a Krebs-Ringer medium collected every 2 min and GH, PRL, TRH, GHRH and SRIH were measured by RIA under basal conditions and in the presence of 10(-6) mol/L DA, TRH or SRIH. Neuropeptides and DA were characterized by HPLC. Both normal and tumoral pituitaries released TRH, SRIH and GHRH in large amounts suggesting their local synthesis. There was an in situ regulation between SRIH and GH as their secretion profile was negatively correlated, GH secretion decreasing while SRIH secretion was increasing. Moreover the release of TRH was stimulated 5 to 20 folds by DA, while PRL decreased at the same time. Pulses of TRH and SRIH had differential effects on GHRH and SRIH release according to the nature of the tissue as TRH stimulated SRIH release from normal pituitary while it inhibited SRIH release from adenoma. These results indicate that anterior pituitary cells can release neuropeptides which are probably endogenously synthesized and have a local regulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

The TSH secretion in the human pituitary adenomas

TSH secretion by a pituitary tumor is very rare (2%) and it is often associated with another hormone: GH or PRL essentially. We present here nine tumors in which the TSH secretion was proved by immunocytochemistry (ICC) and by RIA in the tumor extracts, in the serum and in the culture medium. Four tumors secreted TSH only. Five tumors secreted TSH and GH predominantly. In 3 of them traces of other hormones (PRL and FSH) were also detected. The "pure" TSH adenomas were monomorphous with typical ultrastructural and immunocytochemical features. Plurihormonal TSH adenomas were bimorphous with different cells secreting GH and TSH or monomorphous with one type of cell which secreted TSH or GH or both TSH and GH. In a majority of the cases, the tumoral TSH secretion induced hyperthyroidism but in 2 patients with TSH adenoma there was euthyroidism and in another with TSH-GH adenoma there was no sign of acromegaly and GH serum levels were normal.     

G-protein- and cAMP-dependent L-channel gating modulation: a manyfold system to control calcium entry in neurosecretory cells

Voltage-gated Ca2+ channels are crucial to the control of Ca2+ entry in neurosecretory cells. In the chromaffin cells of adrenal medulla, paracrinally or autocrinally released neurotransmitters induce profound changes in Ca2+ channel gating and Ca2+-dependent events controlling catecholamine secretion and cell activity. The generally held view of these processes is that neurotransmitter-induced modulation of the most widely expressed Ca2+ channels in these cells (N-, P/Q- and L-type) follows two distinct pathways: a direct membrane-delimited Gi/o-protein-induced inhibition of N- and P/Q-type and a remote cAMP-mediated facilitation of L-channels. Both actions depend on voltage, although with remarkably different molecular and kinetic aspects. Recent findings, however, challenge this simple scheme and suggest that L-channels do not require strong pre-pulses to be recruited or facilitated. They are available during normal depolarizations and may be tonically inhibited by Gi/o proteins activated by the released neurotransmitters. Like the N- and P/Q-channels, this autocrine modulation is localized to membrane microareas. Unlike N- and P/Q-channels, however, the inhibition of L-channels is largely independent of voltage and develops in parallel with cAMP-mediated potentiation of channel gating. As L-channels play a crucial role in the control of catecholamine release in chromaffin cells, the two opposite modulations mediated by Gi/o proteins and cAMP may represent an effective way to broaden the dynamic range of Ca2+ signals controlling exocytosis. Here, we review the basic features of this novel L-type channel inhibition comparing it to the well-established forms of L-channel potentiation and voltage-dependent facilitation.     

Neuropeptides of anterior pituitary origin. Autocrine or paracrine functions?

Several neuropeptides classically associated with the hypothalamus have been found in the anterior pituitary. The question arises whether they are locally synthesized and if they play a paracrine or autocrine role on pituitary cell functions. Using normal and tumoral human pituitaries we found neuropeptides (TRH, SRIH, GHRH) and dopamine in variable quantities according to the nature of the tissue. They were all present in normal pituitaries, while stimulatory hormones (TRH and GHRH) were predominantly found in tumoral tissue, implying an imbalance of pathophysiological importance between the stimulatory and inhibitory control of hypophyseal hormones (PRL and GH) in pituitary adenomas. Both normal and tumoral pituitaries released TRH, SRIH and GHRH in large amounts suggesting their local synthesis. The in situ synthesis was demonstrated for SRIH by the evidence of SRIH mRNA, the detection of SRIH immunoreactivity in peculiar cells and the presence of SRIH precursor. The possible role of these pituitary neuropeptides was suggested for instance by the negative correlation found in vitro between SRIH and GH secretions. Moreover, neuropeptides could interact with each other. Indeed DA stimulated TRH release while PRL secretion decrease at the same time. Pulses of TRH had differential effects on SRIH release according to the nature of the tissue as TRH inhibited SRIH release from adenoma while it stimulated SRIH release from normal pituitary. Concerning the effects of SRIH and GHRH on GH secretion, there was an endogenous regulatory pattern comparable to that observed in rat portal blood vessels. Pulses of GHRH induced GH secretion only when endogenous SRIH release was not stimulated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of somatostatin on somatotroph adenomas of the human pituitary: An in vitro functional and morphological study

The effects of somatostatin or the somatostatin analog SMS 201–995 were studied on 4 densely granulated somatotroph adenomas and 4 sparsely granulated somatotroph adenomas in vitro. Release of growth hormone (GH) into culture media during incubation with somatostatin or SMS 201 -995 were measured by radioimmunoassay, and light-microscopical and ultrastructural morphometric parameters were compared with those of cultured control somatotroph adenoma cells of the same tumor. In all tumors except for 1 densely granulated somatotroph adenoma, somatostatin or SMS 201–995 decreased GH release into culture media in 24- and 2-hour incubations. After 48-hour incubation with somatostatin or SMS 201–995, there was no change in cell size or secretory granule diameter. One densely granulated adenoma showed decreased cytoplasmic volume density (CVD) of Golgi apparatus and secretory granules, and a sparsely granulated adenoma had reduced CVD of endoplasmic reticulum. All the tumors that responded with decreased GH release exhibited increased CVD of lysosomes after incubation with somatostatin or SMS 201–995. These results indicate that both densely and sparsely granulated somatotroph adenomas respond to somatostatin inhibition and, furthermore, that inhibition of hormone release is associated with accumulation of lysosomes, suggesting lysosomal degradation of stored hormone. Hospital 20 Nov. (ISSSTE) Coyoacan y Felix Cuevas, Colonia del Valle and (Dept Patologia) y Hospital de Especialidades (C.M.N., IMSS) Cuauhtemoc y Dr. Marquez, Mexico City (IF).     

Growth hormone-releasing hormone expression in pituitary somatotroph adenomas, studied by immunohistochemistry and in situ hybridization using catalyzed signal amplification system

Growth hormone-releasing hormone (GHRH) is a well-known hypothalamic hormone that stimulates the synthesis and release of growth hormone (GH) as well as the proliferation of GH-producing cells in the anterior pituitary gland. Recent reports have shown GHRH synthesis in pituitary somatotroph adenomas, but GHRH immunoreactivity has not been shown in previous studies. To confirm the role of locally generated GHRH for the progression of somatotroph adenomas, we investigated the expression of GHRH in 25 pituitary somatotroph adenomas immunohistochemically, through the use of both conventional avidin-biotin-complex (ABC) method and novel catalyzed signal amplified (CSA) system. In addition, we investigated the expression of GHRH mRNA and GHRH receptor mRNA with in situ hybridization (ISH) using the CSA system. The weak immunopositivity of GHRH was observed in only 2 adenomas (8.0%) of 25 somatotroph adenomas using the ABC method. In contrast, 15 adenomas (60.0%) of 25 somatotroph adenomas were immunopositive for GHRH, as shown by CSA system. Very few of nonsomatotroph adenomas were immunopositive for GHRH using the CSA system. The expression of GHRH mRNA was confirmed, using the CSA-ISH system in 13 adenomas (72.2%) of 18 somatotroph adenomas. In 11 adenomas (61.1%) of 18 somatotrophic adenomas, the expression of GHRH receptor mRNA was demonstrated using the CSA-ISH system. This is a first report that clarified histopathologically GHRH production in pituitary somatotrophic adenomas. The demonstration of GHRH and its receptor expression is meaningful in clarifying the autocrine or paracrine regulation of GHRH in GH production and progression of pituitary somatotroph adenomas.