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1.
Makoto Sugiyama MD Naoko Sanno MD PhD Akira Teramoto MD R. Yoshiyuki Osamura MD PhD 《Endocrine pathology》1998,9(2):125-134
Inhibin and activin are gonadal hormones produced in human ovaries. They are known to act on anterior pituitary cells to regulate
the synthesis and secretion of follicle-stimulating hormone (FSH). The purpose of the present study was to determine the localization
of inhibin and activin subunits α and βA as endocrine markers in the human normal pituitary gland and pituitary adenomas,
using immunohistochemistry andin situ hybridization (ISH) methods.
Pituitary tissues from surgical and autopsy materials were fixed in 10% formalin and embedded in paraffin. Five normal pituitary
glands and 79 pituitary adenomas were immunostained with the avidin-biotin peroxidase complex (ABC) method using polyclonal
antibodies against inhibin and activin subunits α and βA. The other antibodies against anterior pituitary hormones used in
this study were as follows: antigrowth hormone (anti-GH), antiprolactin (anti-PRL), antiadrenocorticotropic hormone (anti-ACTH),
anti-FSHβ, antilutenizing hormone (anti-LH) β, antithyroid-stimulating hormone (anti-TSH) β, and antiglycoprotein α-subunit
(anti-α-SU).
We analyzed gene expressions of subunits α and βA by nonradioisotopic ISH in pituitary adenomas. In the normal human pituitary
glands, inhibin and activin subunits α and βA immunoreactivities were found diffusely in the cytoplasm of anterior pituitary
cells. The percentage of subunit α-immunopositive cells was 40% of the anterior pituitary cells. Subunit βA immunoreactivities
were observed in about 15% of the anterior pituitary cells. By the double-staining method, subunit α immunoreactivity was
detected in all types of anterior pituitary cells, and it was colocalized most frequently with GH and α-SU-positive cells.
Subunit βA immunoreactivity was colocalized predominantly with PRL, FSH-β, LH-β, and α-SU.
Among the 79 adenomas, 75 cases (94.9%) were positive for subunit α, and 50 cases (63.3%) were positive for subunit βA. Subunit
βA was positive in tumor cells with the following incidences: GH adenomas, 3 of 14 (21.4%); PRL adenomas, 5 of 8 (62.5%);
ACTH adenomas, 6 of 6 (100%); TSH adenomas, 7 of 7 (100%); nonfunctioning adenomas, 29 of 44 (65.9%), including gonadotropin-positive,
16 of 22 (80.0%). The ISH signals for subunits α and βA were strongly expressed in gonadotropin-positive adenomas among the
nonfunctioning adenomas. The mRNA signals were low and infrequent in the GH-producing adenomas.
Inhibin and activin subunit α localization did not demonstrate cell-type specificity in pituitary adenomas. In contrast, subunit
βA demonstrated predominant positivity in the functioning pituitary adenomas (ACTH- and TSH-secreting) and nonfunctioning
adenomas (including gonadotropin-positive adenomas). The present results suggest that the functional role of inhibin and activin
in the differentiation of cells in normal human pituitary glands and adenomas is present in subunit βA. 相似文献
2.
3.
In situ hybridization (ISH), which can manifest the specific gene expression of anterior pituitary hormones (mRNA), as well as immunohistochemistry (IHC), is needed to clarify the endocrine function of pituitary adenomas. With the aid of nonisotopic ISH, which has several advantages over isotopic ISH, we examined the expression of pituitary hormone mRNAs in 14 clinically nonfunctioning adenomas, which were considered to be a subtype of gonadotroph adenomas. Gene expression of growth hormone (GH; 4/14), prolactin (PRL; 5/14), adrenocorticotroph hormone (ACTH; 4/14), and gonadotropin were detected with our nonisotopic ISH studies. It is suggested from our ISH studies that some clinically nonfunctioning adenomas are composed of hormone (or subunit) producing cells and may be derived from plurihormonal primordial stem cells. 相似文献
4.
5.
Kovacs K Stefaneanu L Horvath E Buchfelder M Fahlbusch R Althoff PH Moore C 《Endocrine pathology》1996,7(1):91-97
A 64-year-old woman with long-standing Addison’s disease owing to destructive immune adrenalitis presented with hyperpigmentation
and progressively increasing blood adrenocorticotrophic hormone (ACTH) levels. Magnetic resonance imaging demonstrated a pituitary
microadenoma, which was removed by transsphenoidal surgery and investigated by histology, immunocytochemistry, transmission
electron microscopy, andin situ hybridization (ISH). The morphologic studies revealed a basophilic, periodic acid-Schiff (PAS)-positive pituitary adenoma
immunoreactive for ACTh and β-endorphin and in several cells for α-subunit. By transmission electron microscopy, the tumor
was a densely granulated corticotroph adenoma, which, by ISH, expressed pro-opiomelanocortin (POMC) mRNA. The lack of corticotroph
hyperplasia in the nontumorous adenohypophysis was an intriguing finding. Corticotroph adenomas in patients with long-standing
Addison’s disease were very rarely examined by morphology. Our report includes a detailed morphologic analysis and is the
first demonstration of POMC mRNA in the tumor cells using ISH. The question of whether the adenoma was related to increased
secretory activity secondary to protracted hypocorticism or developed independently unrelated to deranged endocrine homeostasis
remains unresolved. The lack of corticotroph hyperplasia in the nontumorous adenohypophysis favors the interpretation that
hypothalamic stimulation played no major role in adenoma formation in our case. 相似文献
6.
Hideko Endo MD Toshiaki Sano MD Shahnaz Begum MD Shozo Yamada MD 《Endocrine pathology》1998,9(2):157-167
Clinically nonfunctioning pituitary adenomas are generally seen in middle-aged and older patients, and most of them may be
gonadotropin-immunoreactive adenomas, that is, gonadotroph adenomas. Our aim was to clarify the relationships between the
gonadotropin immunoreactivity, patient age, sex, and microscopic features in 68 gonadotroph adenomas with special reference
to either gonadotropin-immunonegative or intensively immunopositive adenomas.
There were 68 patients with gonadotroph adenomas (mean age 54.7 yr) in the study, including 39 men (mean age, 52.8 yr) and
29 women (mean age, 57.4 yr). The adenomas were diagnosed on the basis of immunoreactivity for gonadotropins (β-subunit of
follicle-stimulating hormone: β-FSH; β-subunit of luteinizing hormone: β-LH; and the α-subunit of the pituitary glycoprotein
hormone: α-SU) by the avidin-biotin peroxidase complex (ABC) method or by the characteristic histological feature of a perivascular
or pseudorosette pattern, that is, the cells aligned polarity directed toward the capillaries.
Fifty-four adenomas (79%) were positive for one or more gonadotropin subunits and β-FSH was the most common subunit encountered
(47/68, 69%). In men β-FSH immunoreactivity was similar among all age groups, whereas in women, it was significantly less
frequent in patients who were 50 yr or older, compared to younger patients. Gonadotropin-immunonegative adenomas were seen
in 4 men (mean age, 46.8 yr) and 10 women (mean age, 61.5 yr). Among the 22 women aged 50 or over, β-FSH was negative in 12
tumors (55%), whereas in men of the same age group, it was negative in 3 of 26 tumors (12%). The reason for this reduced frequency
is not clear, but the postmenopausal state and associated changes in the systemic endocrine state may play a role.
Adenomas that were intensively positive for β-FSH showed an unusual morphology other than the characteristic perivascular
pattern, regardless of the patients' age and sex; the tumor cells had abundant vacuolated cytoplasms and were arranged in
a sheet-like pattern. Electron microscopically, these cells with abundant cytoplasm had well-developed Golgi complexes, suggesting
an enhanced activity of gonadotropin synthesis, and these adenomas seem to be endocrinologically, if not clinically, functioning.
The results indicate that gonadotroph adenomas may vary from functioning adenomas with intense immunoreactivity and unusual
histology to immunonegative and less functioning adenomas, which are more frequent in women 50 yr or older. 相似文献
7.
Michael Schmid Adrian Münscher Wolfgang Saeger Silke Schreiber Dieter K. Lüdecke 《Pathology, research and practice》2001,197(10):663-669
Null cell adenomas and oncocytomas are clinically inactive adenomas of the pituitary gland. They do not show any significant hormone content detectable by immunohistochemistry. This study aimed at demonstrating mRNAs for all main pituitary hormones in 32 null cell adenomas and 31 oncocytomas by non-isotopic in situ hybridization using digoxigenin-labeled oligonucleotide probes. The results were compared with immunohistochemical and clinical data. Immunohistochemistry (ABC method) was done with monoclonal antibodies against PRL, GH, FSH, LH, TSH, ACTH, alpha-subunit, and Ki-67 (mib-1). The signals for hormone production were detected in both adenoma types in a range from 42% for GH in oncocytomas to 78% for beta-FSH in null cell adenomas. However, these signals are apparently not effective on hormone production, as was shown by almost negative immunostaining. Owing to the simultaneous detection of at least two mRNAs in 78% of null cell adenomas and in 94% of oncocytomas, we assume that both tumor types originate from pluripotential precursor cells that are capable of producing various hormones. According to our data, it is unlikely that the signals influence the clinical behavior. 相似文献
8.
Elke Bäz Wolfgang Saeger Holger Uhlig Susanne Fehr Dieter K. Lüdecke 《Virchows Archiv : an international journal of pathology》1991,418(5):405-410
Summary Within our surgical collection clinically inactive pituitary adenomas represent 30.7% of all pituitary tumours. To characterize their endocrine activity we studied 40 clinically inactive pituitary adenomas with in situ hybridization (ISH) using cRNA probes labelled with35S encoding growth hormone (GH), prolactin (PRL) and chorionic gonadotrophin (HCG). No tumour was associated with clinical evidence of elevated hormone secretion. A mild hyperprolactinaemia not correlated with hormone or the mRNA content of the cells was interpreted to be incidental in 11 patients. By histological analysis, immunohistochemistry (IH) and electron microscopy the adenomas were diagnosed as small cell chromophobic (n=16) and large cell chromophobic (n=8) adenomas, and oncocytomas (n=16). Gene expression of one or more hormones was identified by ISH in 18 of 40 adenomas in few cells. GH and PRL gene expression was rare (GH mRNA in 3 of 40 tumours and PRL mRNA in 8 of 40 tumours) whereas in 14 of 40 adenomasHCG/LH gene expression was identified in scattered cells. Five of 40 adenomas lacking hybridization signals revealed hormones by IH. The detection of mRNA was accompanied by positive immunostaining for the respective hormones in 72%. The combination of ISH and IH reveals good evidence that the hormones are synthesized in the tumours and not taken up from the serum and stored in the cells. The two methods used together permit a more precise analysis of tumour biology than each alone.Presented in part at the meeting on Non-secreting pituitary adenomas, Uppsala, Sweden, May 1990 相似文献
9.
10.
In a series of 40 pituitary adenomas in acromegaly all tumors showed mRNA for GH by in situ hybridization (ISH). The signals were mostly very strong and found in more than 80% of adenoma cells by using frozen sections. In paraffin sections the number of positive cells and the intensity of signals are lower. Prolactin mRNA was found in 87% of adenomas. In 27% more than 80% of cells were marked. beta-HCGmRNA (with 90% hormology for LH-mRNA) was demonstrable in very sparse cells of 25% of adenomas. Comparing ISH with immunohistology (IH) we found a correlation between signals and hormone content in 100% of adenomas for GH, in 60% for Prolactin and in 10% for Gonadotropins. In 18% Prolactin mRNA but not the hormone was demonstrable and in 5% Prolactin was immunostained but no hybridization signals were detected. In a series of 40 clinically inactive adenomas sparse cells of three tumors expressed GHmRNA and two of these contained also the hormone, whereas in one adenoma GH but not GHmRNA was demonstrable. Prolactin mRNA was found in 8 adenomas. 7 of these also contained the hormone. In two cases Prolactin but not Prolactin mRNA was present. Beta-HCG(LH)mRNA and the respective hormones were shown in very sparse cells of 6 adenomas, whereas only beta-HCG(LH)-mRNA was found in 8 cases. The significance of the findings is discussed. 相似文献
11.
Human growth hormone and prolactin secreting pituitary adenomas analyzed by in situ hybridization 总被引:2,自引:2,他引:2 下载免费PDF全文
R V Lloyd M Cano W F Chandler A L Barkan E Horvath K Kovacs 《The American journal of pathology》1989,134(3):605-613
Acidophilic pituitary adenomas commonly produce growth hormone (GH) or prolactin (PRL), according to studies employing immunohistochemical and ultrastructural methods. To examine this question, in situ hybridization with oligonucleotide probes was done on routinely processed tissues received in the pathology laboratory to analyze for the presence of GH and PRL messenger RNA (mRNA) in 4 normal pituitaries, 10 prolactinomas, and 16 GH-secreting adenomas. Most acidophilic cells in normal pituitaries expressed either GH or PRL hormone and the respective mRNAs, but GH mRNA and PRL hormone were also detected in some of the same cells. Patients with a clinical diagnosis of prolactinoma had cells with only PRL mRNA in their tumors, while most (14 of 16) patients with a clinical diagnosis of acromegaly or gigantism had both GH and PRL mRNAs in their tumors. The GH adenomas varied in these studies. In situ hybridization was helpful in characterizing the adenoma from a patient with acromegaly who had immunoreactive PRL, but no immunoreactive GH in the resected tumor; in situ hybridization analysis revealed mRNAs for both GH and PRL in the same tumor cells. Our findings indicate that pituitary adenomas from patients with acromegaly commonly express PRL mRNA. It is concluded that in situ hybridization provides new information about the clinical biology and the histopathologic classification of pituitary adenomas. 相似文献
12.
Lucia Stefaneanu Kalman Kovacs Eva Horvath Ricardo V. Lloyd 《Virchows Archiv : an international journal of pathology》1991,419(2):107-113
Summary Pro-opiomelanocortin (POMC) mRNA was detected on paraffin sections by in situ hybridization (ISH) in corticotrophs of 12 nontumorous pituitaries, 11 functioning corticotroph, and 11 silent pituitary adenomas. ISH combined with immunocytochemistry for adrenocorticotrophic hormone (ACTH), a POMC-derived peptide, was also performed. ACTH immunoreactive cells of the anterior lobes and those invading the posterior lobe showed a high or moderate level of POMC mRNA that was not correlated with the intensity of ACTH immunoreactivity. Variable levels of POMC gene expression were present in Crooke's cells, corticotrophs suppressed by glucocorticoid excess. Most functioning corticotroph adenomas and silent subtype 1 adenomas had an intense hybridization signal and ACTH immunoreactivity. In silent subtype 2 and 3 adenomas, POMC mRNA had a diffuse low level or was absent; in these adenomas ACTH immunoreactivity was diffuse, restricted to some cells, or negative. The results indicate that POMC gene is expressed in both normal and suppressed nontumorous corticotrophs. Intense signals for POMC mRNA are found in most functioning corticotroph adenomas. The difference between POMC gene expression in silent 1 and silent 2 and 3 adenomas suggests that different mechanisms are responsible for the lack of endocrine activity. 相似文献
13.
14.
Naritaka H Kameya T Sato Y Furuhata S Okui J Kamiguchi Y Otani M Toya S 《Endocrine pathology》1995,6(3):239-246
We report a case of giant pituitary adenoma in a child. Computerized tomography (CT) scan revealed a suprasellar extension
tumor mass with hydrocephalus. There was no clinical evidence of acromegaly, gigantism, and other hormonal symptoms. Endocrinologic
studies showed within normal value of serum growth hormone (GH: 4.2 ng/mL) and slightly increased levels of prolactin (PRL:
78 ng/mL) and other pituitary hormone values were within normal range. On suppression test by bromocryptin, both GH and PRL
levels were reduced. Histopathological findings revealed that the tumor consisted of predominantly chromophobic and partly
eosinophilic adenoma cells. Immunohistochemical staining detected GH and PRL in a small number of distinctly different adenoma
cells, respectively. Nonradioactivein situ hybridization (ISH) also showed GH and PRL mRNA expression in identical immunopositive cells. Electron microscopy (EM) demonstrated
adenoma cells with moderate or small numbers of two types of dense granules and without fibrous body which are characteristic
of sparsely granulated GH-cell adenomas. The adenoma does not fit into any classification but may be an atypical acidophil
cell line tumor showing focal differentiation toward both GH and PRL cells. 相似文献
15.
Tampanaru-Sarmesiu A Kovacs K Singer W Stefaneanu L Thapar K Wroblewski J 《Endocrine pathology》1996,7(3):237-243
A 74-year-old man presented in a near terminal state with progressive generalized muscular weakness, gastrointestinal disturbances,
and lethargy. Investigations revealed hypotension, hyponatremia, hypoglycemia, and low plasma cortisol concentration accompanied
by undetectable plasma adrenocorticotropic hormone (ACTH) level. The patient died shortly after admission to hospital, with
adrenocortical failure being the provisional cause of death. Autopsy disclosed profound bilateral atrophy of adrenal cortices
with evidence of a mild focal inflammatory reaction. The pituitary gland appeared normal on both gross and histologic examinations.
There was no histologic evidence of inflammation, fibrosis, or adenohypophysial cell hyperplasia. By immunocytochemistry,
no ACTH and β-endorphin immunoreactive cells were identified in the adenohypophysis.In situ hybridization (ISH) for pro-opiomelanocortin (POMC) mRNA yielded conclusively negative results. The case presented here was
regarded as isolated ACTH deficiency. Although the remaining pituitary functions were not assessed, clinical and morphologic
findings strongly support the supposition that aside from ACTH deficiency, secretory function of other pituitary hormones
was preserved. This is the first case in which the pituitary was studied by immunocytochemistry and ISH. The possible pathogenetic
mechanisms accounting for the isolated ACTH deficiency are discussed. 相似文献
16.
Analysis of endocrine active and clinically silent corticotropic adenomas by in situ hybridization. 下载免费PDF全文
R. V. Lloyd K. Fields L. Jin E. Horvath K. Kovacs 《The American journal of pathology》1990,137(2):479-488
The distribution of pro-opiomelanocortin (POMC) messenger RNA (mRNA) in 7 functional and 17 clinically silent corticotropic adenomas was analyzed by in situ hybridization (ISH) with 35S-labeled oligonucleotide probes using formalin-fixed paraffin-embedded tissue sections cut from blocks that were in storage between 1 to 14 years. All 7 functional adenomas and 4 subtype 1 tumors had detectable POMC mRNA, while 3 of 6 subtype 2 and 1 of 7 subtype 3 silent adenomas contained detectable POMC mRNA. In situ hybridization analysis with an 35S-labeled beta-actin probe showed a positive hybridization signal in 22 of 22 cases, indicating that the absence of detectable POMC mRNA in some adenomas was not due to loss of the mRNAs during processing of the tissues or because of the age of the embedded tissue blocks. Northern hybridization analysis with the oligonucleotide probes in 2 normal pituitaries and an adenoma causing Cushing's disease detected a 1.2-Kb mRNA in all three tissues, indicating that the oligonucleotide probes were very specific. These results indicate that subtype 1 silent adenomas and clinically active adenomas associated with Cushing's disease contain POMC mRNA that is readily detectable by ISH in routinely processed tissue specimens, while only a few of the subtypes 2 and 3 adenomas have POMC mRNA that can be detected in paraffin blocks with the oligonucleotide probes used in this study. 相似文献
17.
Shunichi Yokoyama Kamal Thapar Kalman Kovacs L. Stefaneanu 《Virchows Archiv : an international journal of pathology》1998,432(3):241-246
Insulin-like growth factors (IGFs) have been reported to promote cell proliferation in many tumours, but their contribution to pituitary adenoma development and growth has not been characterized. We report the presence of insulin-like growth factor II (IGF-II) mRNA in pituitary adenomas using in situ hybridization (ISH). The intensity of IGF-II hybridization signal was correlated with adenoma type, and the presence of Ki-67. Among the 109 adenomas examined, 55 (50.4%) were positive for IGF-II mRNA. All acidophil stem cell, functioning corticotrophic and plurihormonal adenomas contained the message; a high incidence of signal was found among sparsely (7/8) and densely (4/6) granulated growth hormone (GH) cell adenomas, mixed GH cell–prolactin (PRL) cell adenomas (6/7), thyrotrophic (4/6) and null-cell (6/7) adenomas. Less frequently, IGF-II mRNA was localized in mammosomatotrophic, silent subtype 3, gonadotrophic, and oncocytic adenomas, whereas all sparsely granulated PRL cell adenomas and silent corticotrophic adenomas of subtypes 1 and 2 were negative. The MIB-1 labelling index was significantly higher in adenomas with a moderate to intense IGF-II signal than in adenomas with weak or no signal. The results suggest that IGF-II, when highly expressed, may have a role in pituitary adenoma proliferation. 相似文献
18.
Scheithauer BW Kovacs KT Stefaneanu L Horvath E Kane LA Young WF Lloyd RV Randall RV Davis DH 《Endocrine pathology》1995,6(3):173-187
To compare the pituitary pathology of gigantism to that of acromegaly, 19 surgically resected lesions were studied from 10
males and 9 females, ages 13–49 (mean, 19 yr) with excessive height (≥95th percentile), onset of disease prior to puberty,
elevated growth hormone (GH) levels despite glucose suppression, and a pathologically confirmed GH-producing pituitary mass.
One patient had MEN-I. The lesions included 18 adenomas and 1 case of pure hyperplasia. The median, mean, and range of serum
GH and prolactin (PRL) levels were 64, 235, 5–1000 ng/mL and 47, 146, 29–770 ng/mL, respectively. Of the 8 adenoma specimens
accompanied by nontumoral pituitary (i.e., tissue wherein the presence of hyperplasia was assessable), 3 (37%) demonstrated
both. Of the 18 tumors, 78% were macroadenomas and 22% were grossly invasive; their immunophenotypes included GH (5%), GH
and PRL (19%), and GH-PRL and a glycoprotein hormone, usually TSH and/or α-subunit (76%). Of the 10 adenoma-containing lesions
subject to electron microscopy (EM), 2 consisted of GH cells alone; 2 of mammosomatotroph (MS) cells alone; 1 of GH and MS
cells; 1 of GH and PRL cells; 2 of GH, PRL, and MS cells; 1 of GH, PRL, and glycoprotein cells; and 1 was a subtype 3 adenoma.
Ultrastructurally, GH cells and/or MS cells predominated in these lesions. Immuno-EM of one GH and PRL cell and of one GH-PRL-MS
tumor showed GH and PRL to be present not only in single cells but within the same granules. Nine of 12 adenoma-associated
lesions subject to combinedin situ hybridization (ISH) and immunostaining showed double labeling for PRL (or GH) mRNA and for GH (or PRL), respectively, features
indicating MS differentiation. In the 4 lesions exhibiting hyperplasia, either alone (1) or in association with adenoma (3),
EM showed MS cells in 3, and immuno-EM as well as combined immunohistochemistry and ISH showed double labeling for GH and
PRL in both of the 2 cases studied. In summary, although in terms of their tinctorial characteristics and tumor size, the
lesions of giants resemble those of acromegalics, those of the former are less often invasive and glycoprotein hormone containing,
and more often contain ultrastructurally distinctive MS cells. The high frequency of adenoma with hyperplasia (37%) and the
occurrence of hyperplasia alone (6%) is of particular notice since this finding is rare in patients with acromegaly. Hyperplasia
is, however, seen in ectopic GH-releasing hormone production and the McCune-Albright syndrome. We conclude that the presence
of MS is not rare in the pituitary lesions of patients with gigantism. Their presence may be a reflection of either hypothalamic
dysfunction or of an intrinsic abnormality of pituitary cells. 相似文献
19.
20.
Growth hormone (GH) and prolactin (PRL) gene expression and immunoreactivity in GH- and PRL-producing human pituitary adenomas 总被引:3,自引:0,他引:3
Jie Li Lucia Stefaneanu Kalman Kovacs Eva Horvath Harley S. Smyth 《Virchows Archiv : an international journal of pathology》1993,422(3):193-201
Summary Growth hormone(GH)-producing pituitary adenomas are morphologically heterogeneous and frequently contain not only GH immunoreactivity but also variable numbers of prolactin (PRL) immunopositive cells. Paraffin sections of 59 surgically removed GH- and/or PRL-producing adenomas classified by histology, immunocytochemistry (ICC) and electron microscopy were studied using in situ hybridization (ISH) for GH and PRL mRNA and combined with ICC for the coded hormones. Somatotroph adenomas (10 densely and 10 sparsely granulated tumours) and mammosomatotroph adenomas (10 cases) contained both GH mRNA and GH immunoreactivity. In 4 densely and 4 sparsely granulated somatotroph adenomas and 4 mammosomatotroph adenomas, only GH mRNA and its product were found. In 28 cases (6 densely and 6 sparsely granulated somatotroph adenomas, 10 mixed somatotrophlactotroph adenomas and 6 mammosomatotroph adenomas) both GH and PRL mRNA were present, although no PRL immunoreactivity was not in 2 densely granulated somatotroph adenomas. In these cases, ISH for PRL mRNA combined with GH immunostaining revealed the presence of variable numbers of mammosomatotrophs. In 9 acidophil stem cell adenomas only PRL mRNA and its product were found; one tumour expressed both GH and PRL mRNA and their products. Nine lactotroph adenomas contained only PRL mRNA and PRL immunoreactivity. The results show that GH and/or PRL mRNA content could not be correlated with ICC for coded proteins and ultrastructural features. The mammosomatotrophs were more numerous using ISH when compared with ICC. Somatotroph, mammosomatotroph and mixed adenomas are closely related and they can be considered to represent one basic tumour type originating in a cell committed to GH production. This may undergo clonal differentiation towards a mammosomatotroph and further to the lactotroph line. The results also indicate that lactotroph adenomas arise in a cell committed to PRL production. Acidophil stem cell adenomas seem to be more closely related to lactotroph cells than somatotroph. 相似文献