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At least 19 recordsLinked to original sources

Effect of the isolated removal of the median eminence (ME) and pituitary stalk (PS) on the immunohistology and hormone release of the anterior pituitary gland grafted into the hypophysiotrophic area (HTA) and/or of the in situ pituitary gland.

Isolated removal of the median eminence (ME) and pituitary stalk (PS) of female rats was performed under visual control, using a new instrument to open up the 3rd ventricle. Atrophy of the uterus, the follicles and the intersitial tissue in the ovaries was accompanied by persistent corpora lutea and persistent diestrous vaginal smears in rats which had undergone a successful removal of ME and PS. No change was, however, detected in the weight of the thyroid and adrenal glands at the end of the six weeks experimental period. An adenohypophysis implanted in the place of the ME at the time of the surgery, could not prevent these changes. In animals, in which the removal of the ME was not complete, the changes of the gonadal system were less pronounced. Immunocytology of the pituitary LH-, FSH, TSH- and prolactin-cells in animals with completely removed ME and PS showed inactive LH- and FSH-cells both in the grafted and in situ pituitaries, while the TSH- and prolactin-cells appeared to be in a stimulated state. In animals with ME remnant, LH-RH axon terminals were localized only on the blood vessels of the remnant. The part of the pituitary graft in contact with these blood vessels, as well as some areas of the in situ pituitary gland, contained active LH cells as judged from their size and immunohistological appearance. Since in the absence of the ME, the hypophysiotrophic area is not able to exert its regulatory effect on the gonadotrophs of the pituitary implant in this area, the authors suggest that this effect is mediated by the blood circulation of the ME which is rich in releasing hormones and is drained toward both the anterior pituitary and the medial basal hypothalamus.

Animals

Tissue culture studies on human pituitary tumours: long term release of anterior pituitary hormones into the culture medium.

A study was undertaken to determine the length of time that human pituitary tumours are capable of releasing anterior pituitary polypeptide hormones in vitro under basal conditions and to study the spectrum of hormone release by functioning and "non-functioning" pituitary neoplasms. Fragments from the pituitary tumours of 10 patients in the following categories: 1 Cushing's disease, 2 with amenorrhoea-galactorrhoea, 3 with acromegaly, and 4 with "non-functioning" pituitary tumours and from 2 normal human anterior pituitary glands were placed in primary culture immediately after surgery. The in vitro release of human growth hormone (hGH), prolactin (Prl), thyrotrophin (TSH), adrenocorticotrophin (ACTH), luteinizing hormone (LH), and follicle stimulating hormone (FSH) was measured by specific radioimmunoassays at the end of each week in culture. Hormone release was surveyed from 6 weeks to 6 months depending upon the survival of the culture. Hormone release patterns were compared with clinical and pathological data. In the initial week of the study, all 6 anterior pituitary polypeptides were detected in the media from the 2 control pituitaries and from 4 of the tumours (1 amenorrhoea-galactorrhoea and 3 acromegaly) in concentrations up to 100 ng/ml of medium while 5 of the 6 hormones were readily detectable in the media from 2 additional tumour samples (Cushing's disease and 1 "non-functioning" pituitary tumour). The media of the remaining 4 tumours contained at least 3 of the 6 hormones (1 amenorrhoea-galactorrhoea and 3 "non-functioning" pituitary tumours). After 6 months in culture, the 6 hormones were readily detectable in at least 1 of the 5 surviving cultures and hGH (up to 800 ng/ml) and LH were each detectable in the media from 2 cultures. Although most of the hormone concentrations in the media decreased with length of time in culture, there were 2 exceptions. First in the media from 5 of the 12 cultures from both controls and tumours, Prl concentrations increased after 50 to 80 days culture. This increase usually lasted for several weeks before Prl levels again began to decline. The second unusual finding occurred in a tumour from a patient with acromegaly in the media of which hGH levels rose from 60 ng/ml to 800 ng/ml between days 125 and 174. These findings of prolonged hormone release in vitro give promise of future usefulness of tissue culture methods for study of polypeptide hormone releasing mechanisms and long-term production of human anterior pituitary hormones for use in research and possible therapy.

Acromegaly

Some biochemical characteristics of hormone-secreting pituitary tumors and of the host's anterior pituitary gland.

The activity of some glycolytic, oxidative, and degradative enzymes was studied in transplanted rat hormone-secreting pituitary tumors MtTW15 and 7315a and in the host pituitary gland. The elevated serum-hormone concentrations produced by 7315a tumor decreased the size of the host's pituitary gland, its hormone content, and G6P-DH, LDH, PK, and ICDH, but produced no changes in MDH, acid phosphatase, cathepsin-D, and LYSAR enzyme activities (mU/mg tissue). LDH and PK activities were greater in unit weight of pituitary tumors than in pituitary glands. Although more G6P-DH was found in MtTW15 tumor than in normal pituitary tissue, less of the enzyme was detected in 7315a pituitary tumor. It is concluded that elevated serum pituitary hormones selectively decrease hormone production and the activity of some enzymes in the pituitary gland, presumably through a feedback mechanism.

Animals

Contributions of plasma triiodothyronine and local thyroxine monodeiodination to triiodothyronine to nuclear triiodothyronine receptor saturation in pituitary, liver, and kidney of hypothyroid rats. Further evidence relating saturation of pituitary nuclear triiodothyronine receptors and the acute inhibition of thyroid-stimulating hormone release.

Injections of triiodothyronine (T(3)) and thyroxine (T(4)) into chronically hypothyroid rats were used to evaluate the contribution of intracellular T(4) to T(3) conversion to nuclear T(3) in pituitary, liver, and kidney, and to correlate the occupancy of pituitary nuclear T(3) receptors with inhibition of thyroid-stimulating hormone (TSH) release. Injection of a combination of 70 ng T(3) and 400 ng T(4)/100 g body wt resulted in plasma T(3) concentrations of 45+/-7 ng/dl (mean+/-SD) and 3.0+/-0.4 mug/dl T(4) 3 h later. At that plasma T(3) level, the contribution of plasma T(3) to the nuclear receptor sites resulted in saturation of 34+/-7% for pituitary, 27+/-5% for liver, and 33+/-2% for kidney. In addition to the T(3) derived from plasma T(3), there was additional T(3) derived from intracellular monodeiodination of T(4) in all three tissues that resulted in total nuclear occupancy (as percent saturation) of 58+/-11% (pituitary), 36+/-8% (liver), and 41+/-11% (kidney), respectively. The percent contribution of T(3) derived from cellular T(4) added 41% of the total nuclear T(3) in the pituitary which was significantly higher than the contribution of this source in the liver (24%) or the kidney (19%). 3 h after intravenous injection of increasing doses of T(3), the plasma T(3) concentration correlated well with both the change in TSH and the nuclear occupancy, suggesting a linear relationship between the integrated nuclear occupancy by T(3) and TSH release rate. The contribution of intrapituitary T(4) to T(3) conversion to nuclear T(3) was accompanied by an appropriate decrease in TSH, supporting the biological relevance of nuclear T(3). Pretreatment of the animals with 6-n-propylthiouracil before T(4) injection decreased neither the nuclear T(3) derived from intrapituitary T(4) nor the subsequent decrease in TSH. These results indicate that intracellular monodeiodination of T(4) contributes substantially to the nuclear T(3) in the pituitary of the hypothyroid rat, and suggest a linear inverse relationship between nuclear receptor occupancy by T(3) in the pituitary and TSH release rate. The data further indicate that T(4) to T(3) monodeiodination is considerably more important as a source of nuclear T(3) in the pituitary than in the liver and kidney. This provides a mechanism whereby the TSH secretion could respond promptly to a decrease in thyroid secretion (predominantly T(4)) before a decrease in plasma T(3) would be expected to lead to significant metabolic hypothyroidism.

Animals

High molecular weight forms of adrenocorticotropic hormone in the mouse pituitary and in a mouse pituitary tumor cell line.

Denaturing solvents have been used to determine the molecular weight of the adrenocorticotropic hormone (ACTH) activity in mouse pituitary, in an ACTH secreting mouse pituitary tumor cell line (AtT-20/D-16v), and in the tissue culture medium from the pituitary tumor cells. ACTH activity was quantitated by radioimmunoassay and by bioassay. It is possible to utilize guanidine hydrochloride or sodium dodecyl sulfate in characterizing the multiple forms of ACTH because treatment of porcine ACTH (the 39 amino acid polypeptide form of ACTH, alpha(1-39)), pituitary extracts, tumor cell extracts, and tumor cell tissue culture medium with these denaturants does not diminish the immunological ACTH activity. Based on gel filtration in the presence of guanidine hydrocholoride, extracts of the pituitary tumor cells and the mouse pituitary contain three distinct molecular weight classes of ACTH activity. The major form of ACTH has a molecular weight similar to alpha(1-39) (molecular weight 4000-5500), but there are significant amounts of two higher molecular weight forms of ACTH: molecular weight 6500-9000 and molecular weight 20,000-30,000. The 6500-9000 molecular weight form of ACTH is the major form of ACTH in the tissue culture medium; there is no peak of alpha(1-39) size ACTH in the medium. In the radioimmunoasay all three forms of ACTH generate competitive binding curves parallel to that of porcine alpha(1-39); in the bioassay (stimulation of steroidogenesis in a mouse adrenal tumor cell line) the dose response curve for each of the molecular forms of ACTH is parallel to that for porcine alpha(1-39).

Adrenocorticotropic Hormone

Pituitary responsiveness to synthetic LH-RH and pituitary LH content at various reproductive stages in the sheep.

In sheep the basal concentration of LH in jugular vein plasma was significantly higher during the first 50 days of gestation in late pregnancy or at parturition. The pituitary response to a single i.v. injection of 200 microng synthetic LH-RH was determined at different stages of gestation and compared with that of anoestrous and cyclic sheep. Pituitary response to LH-RH decreased progressively with advancing gestation: by 56 days after mating the response had declined to 35% and by parturition to 14% of the value in anoestrous sheep. The pituitary response to LH-RH increased after parturition and the pattern of recovery differed in non-lactating and lactating sheep. By 63 days postpartum the response to LH-RH in non-lactating and lactating animals had returned to values similar to those in sheep during anoestrus and sheep during the luteal phase of the oestrous cycle. A decrease in pituitary responsiveness during pregnancy was associated with a decrease in pituitary content of LH. The quantity of LH released in response to a standard injection of LH-RH was linearly related to pituitary LH content.

Animals

Prolactin-secreting pituitary adenomas in women. II. Menstrual function, pituitary reserves, and prolactin production following microsurgical removal.

A prospective study of 46 women with prolactin-secreting pituitary adenomas and amenorrhea and/or galactorrhea was performed to determine the influence of the selective transsphenoidal removal of these tumors on pituitary and reproductive function. This procedure was effective in restoring menstrual function in 34 of 41 women and in eliminating lactation in 30 of 40 women. Tumor size and preoperative serum prolactin concentrations were the most important factors in predicting the postoperative disappearance of symptoms. Normal menstrual function returned in 33 of 34 women with tumors less than 2 cm in diameter but in only one of seven women with tumors greater than 2 cm. Similarly, galactorrhea disappeared in 29 of 34 women with tumors less than 2 cm but in only one of six women with larger tumors. Menses returned in 31 of 32 women and galactorrhea disappeared in 25 of 31 women with preoperative serum prolactin levels below 200 ng/ml; conversely, menses returned in only three of nine women and lactation ceased in one of six women with preoperative serum prolactin concentrations above 200 ng/ml. Prolactin concentrations decreased in 42 of 43 patients following the removal of pituitary adenomas and returned to normal in 30. Postoperative pituitary reserves of adrenocorticotropic hormone, growth hormone, luteinizing hormone, and follicle-stimulating hormone were normal in most patients. These data indicate that the removal of prolactin-secreting pituitary adenomas by a neurosurgeon accomplished in this surgical technique is effective in restoring menstrual function and eliminating lactation in most women, especially if the tumor is less than 2 cm in diameter and the preoperative serum prolactin concentration is less than 200 ng/ml.

Adenoma

Studies on the pituitary "fettstoffwechselhormon". VI. Preparation of two highly purified lipolytic active peptides from hog pituitary glands.

The preparation of two highly purified lipolytically active hog pituitary peptides, called P-LF II C and P-LF II D is described. The two peptides are free of other pituitary hormone activities. In isolated rat and porcine adipose tissue, both fractions are lipolytically much more active than every other lipolytic active pituitary peptide described to date. By fraction P-LF II D, the first pituitary peptide was isolated which has lipolytic activity in isolated rat adipose tissue than corticotropin, the lipolytically most active pituitary hormone known so far. On isolated porcine adipose tissue, fraction P-LF II D as well as P-LF II C showed without doubt higher activity than corticotropin.

Adipose Tissue

Pituitary autonomy in hyperprolactinemic secondary amenorrhea: results of hypothalamic-pituitary testing.

Twenty-seven women with secondary amenorrhea of greater than six months duration were subjected to multiple testing of hypothalamo-pituitary function. They were divided into normo-prolactinemic (Group 1 mean serum prolactin (PRL) 9.8 ng/ml; range 6.8 to 13.0 ng/ml; n=9) and hyperprolactinemic (Group 2 mean 37.5 ng/ml; range 19.2 to 93.7 ng/ml; n=18) groups on the basis of 4 weekly baseline determinations. Group 2 had significantly (P less than .05) lower serum LH and urinary pregnanediol levels than did Group 1; there was no statistical difference between the groups in serum FSH, T4, T3 or urinary estrogen measurements. Two women in Group 2 were found to have a pituitary chromophobe adenoma. Group 2 women showed no significant rises in serum PRL following stimulation tests with thyrotropin releasing hormone (TRH, 200 microng iv) and metoclopramide (10 mg orally), which caused significant responses in Group 1. The TSH response to TRH was, however, preserved in Group 2, while it was subnormal in Group 1 subjects. Both groups showed similar FSH and LH responses to luteinizing hormone-releasing hormone (LHRH, 25 microng iv). No significant suppression of serum PRL was seen in Group 2 patients given L-Dopa (500 mg orally),, which produced a significant response (P less than 0.05) in Group 1 subjects, while all patient showed marked reduction in serum PRL values following 2-bromo-alpha-ergocryptine (CB-154, 2.5 mg orally). When compared with other Group 2 members, the 2 cases with proven pituitary adenomata gave similar responses to the stimulation-inhibition tests and were not clearly distinguished on this basis. We conclude: 1. The pattern of PRL responses to dynamic tests, although of pathophysiological interest an autonomous pituitary lesions in patients with hyperprolactinemic secondary amenorrhea. 2. Such dynamic tests, although a pathophysiological interest, provide no clinical information additional to that provided by the mean basal serum PRL value. 3. In clinical practice, such dynamic tests should be confined to patients with mean serum PRL levels at around the upper limit of the normal range.

Adult

Anterior pituitary function before and after trans-sphenoidal microsurgical resection of pituitary tumors.

Anterior pituitary lobe function was measured pre- and postoperatively in 40 patients with pituitary tumors who were managed surgically by the trans-sphenoidal approach. Of 23 patients with normal anterior lobe function preoperatively, 21 (91%) were normal postoperatively. Of 17 preoperatively impaired patients, 7 (40%) regained normal function, 3 (18%) improved, 4 (24%) remained the same, and 3 (18%) were further impaired by the surgery. In this small series, the likelihood of recovery of pituitary function varied inversely with the degree of preoperative impairment and the size of the tumor, suggesting that more aggressive surgical management of small, minimally symptomatic pituitary tumors is justified.

Adenoma

Collection of blood from the pituitary stalk and portal veins in monkeys, and from the pituitary sinusoidal system of monkey and man.

A transorbital, transsphenoidal microsurgical approach to the pituitary stalk and gland was used to collect blood from the hypothalamo-hypophyseal portal system in monkeys. Specimens may be obtained from the entire pituitary stalk, individual long portal veins, or the pituitary sinusoidal bed, with little risk of mortality. Continuous stalk blood sampling was carried out for periods of up to 10 hours. Pituitary sinusoidal-system blood was also collected during transsphenoidal surgery in man. The uses of data concerning hypothalamic-hypophyseal regulation obtained by these methods are illustrated.

Animals

Hypothalamo-pituitary-adrenal function in pituitary adenoma and craniopharyngioma. Part I: Insulin test, lysine-vasopressin test, and rapid ACTH test.

For the assessment of hypothalamo-pituitary-adrenal function in the presence of pituitary adenomas and craniopharyngiomas, insulin tests, lysine-vasopressin tests, and rapid ACTH tests were performed and plasma cortisol was assayed. Rapid ACTH test and lysine-vasopressin test, which examine adrenal and mainly pituitary function respectively, showed normal function in ten among 14 cases. But insulin test, which examines the whole hypothalamo-pituitary-adrenal function, showed various levels of abnormality in eight among 14 cases. Frequent association of functional disturbances of this axis in these diseases was stressed.

Adenoma, Chromophobe

[Specific role of sex steroids on the pituitary level. Sex steroids and anterior pituitary secretion].

Although sex steroids were known to play a role in the control of LH, FSH, TSH and prolactin secretion, in vivo experiments could not discriminate between hypothalamic and pituitary sites of action. In this study, the specific action of sex steroids at the anterior pituitary level could be achieved using rat adenohypophyseal cells in primary culture. While estrogens stimulated the sensitivity of the LH and FSH responses to LHRH, androgens had differential effects on the secretion of the two gonadotropins: marked inhibition of LH and stimulation of FSH secretion. Progesterone, on the other hand, while having no effect in the absence of estrogens, could reverse the stimulatory effect of estrogens on LH release while it led to a stimulation of FSH secretion. Estrogens and thyroid hormone exert respective stimulatory and inhibitory effects on TSH secretion by a direct action at the pituitary level. These effects appear to be mediated changes of the level of adenohy-pophyseal TRH receptors. A close correlation was observed between the specificity of binding of the dopamine agonist (3H)dihydroergocryptine and the control of prolactin release in cells in culture, thus supporting the physiological importance of the dopamine receptor in the control of prolactin release. The high degree precision of this system permits assessment of activity of not only dopamine agonists and antagonists, but also of compounds having mixed agonist-antagonistic activity. Preincubation of anterior pituitary cells with 17beta-estradiol not only stimulated basal and TRH-induced prolactin release but, more unexpectedly, led to an almost complete reversal of the inhibitory effect of dopamine agonists on prolactin secretion. Besides its own interest, the adenohypophyseal cell culture system could well be used as a model system for study of the interaction between estrogens and dopaminergic action.

Androgens

Biosynthesis of gonadotropins by rat pituitary cells in culture and in pituitary homogenates: effect of gonadotropin-releasing hormone.

The incorporation of labeled amino acids and glucosamine into LH and FSH by cultured rat anterior pituitary cells and anterior pituitary homogenates is reported. There was a significant augmentation in this incorporation by cells after 6 days of culture in the presence of GnRH. Tritiated LH and FSH were found in the cell extracts as well as in the media by the method of immunoprecipitation. An increase of approximately 7--13-fold in the release of LH and FSH into the cell incubation medium was observed in the presence of GnRH (3 ng/ml). The rate of incorporation of [3H]proline was higher than that of [3H]glucosamine into LH and FSH. At the same time a higher incorporation of labeled amino acids was observed in the case of FSH than with LH. Cycloheximide inhibited completely the incorporation of labeled proline but the inhibition was partial for the incorporation of labeled glucosamine. Freshly dispersed cells, short-time cultures maintained for 20 h and pituitary homogenates also incorporated labeled amino acids into LH and FSH, but GnRH had no effect on this incorporation. Pituitary homogenates also incorporated [3H]glucosamine into LH and FSH with an optimal incorporation after 30 min of incubation. Three different concentrations of GnRH had no effect on the incorporation of [3H]proline by homogenates. Cycloheximide and puromycin inhibited this incorporation completely.

Amino Acids

ADH release from cut pituitary stalk and intact pituitary gland during amygdala stimulation at various frequencies in rats.

Changes in antidiuretic substance (i.e., vasopressin) release from the cut pituitary stalk and the intact pituitary gland were observed during electrical stimulation of amygdala medial nucleus. Electrical pulses of 4 or 36 cycles per second (cps) were used and in both cases the same energy (about 2.160 nanowatt seconds) per 1.5 sec-train of electrical pulses remained constant. Antidiuretic substance release from the hypothalamic end of the cut pituitary stalk and from the intact pituitary gland increased during the 36-cps electrical stimulation of amygdala medial nucleus, however the 4-cps electrical stimulation of this structure did not produce any changes in these processes. The results obtained indicate that the medial nucleus of amygdala is able to change the function of the hypothalamo-hypophysial system and can be motivated with high frequency stimulating pulses.

Amygdala

Pituitary Neuroendocrine Tumor or Pituitary Adenoma? Let's Ask the Epigenome!

The introduction of the term pituitary neuroendocrine tumor (PitNET) to replace pituitary adenoma has sparked a versatile debate among experts. The controversy surrounding this nomenclature change includes the question of whether these tumors' biological identity truly corresponds to neuroendocrine tumors. In this meta-analysis, DNA methylation data were interrogated to clarify whether the old or new nomenclature more accurately reflects the epigenome of these tumors. Publicly available DNA methylation data of 100 NETs, 100 PitNETs/adenomas, and 100 adenomas of various origins and lineages were compiled from 18 different publications. Epigenomic signatures characteristic of NETs and adenomas were defined and compared to those of PitNETs/adenomas. Promoter CpG methylation levels were investigated for hallmarks of cellular differentiation. Comparative DNA methylation analyses demonstrated that all 100 PitNETs/adenomas aligned more closely with NETs than with adenomas. Focusing on promoter-associated CpGs moreover confirmed robust epigenomic features associated with neuroendocrine differentiation in PitNETs/adenomas. These findings indicate that PitNETs/adenomas resemble NETs rather than adenomas on the epigenomic level and support PitNET as the biologically more accurate term. Of note, appropriately addressing the broad spectrum of clinical behaviors in these tumors remains a critical issue in the current pituitary tumor classification framework and nomenclature.

Humans

Relationship between plasma prolactin concentration and pituitary function in patients with a pituitary adenoma.

The influence of hyperprolactinaemia on endocrine functions in forty-two consecutive patients with untreated pituitary tumours was studied. Patients with acromegaly, Cushing's disease and Nelson's syndrome were excluded. Sixteen patients (eleven men and five women) had a pituitary adenoma with suprasellar extension and twenty-six (eleven men and fifteen women) had a small intrasellar tumour. Basal plasma prolactin concentration was measured in all. Thyroid function was assessed by plasma thyroxine (T4) and TSH concentrations, adrenocortical function and growth hormone (GH) secretion by the maximum plasma cortisol, adrenocorticotrophin (ACTH) and GH concentrations, respectively, during insulin-induced hypoglycaemia (tITT). Gonadal function was studied by measuring plasma concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol-17 beta and in men, testosterone. On the basis of computer assisted tomography of the sella turcica, the tumour volume was calculated. The basal plasma prolactin concentration was elevated in 69% of the patients. Decreased GH secretion was the most frequent pituitary dysfunction (78%) followed in men by gonadal insufficiency (77%), adrenocortical insufficiency (31%) and thyroid insufficiency (21%). There was no difference between patients with elevated and normal plasma prolactin concentration as to the tumour volume and any of the endocrine variables.

Adenoma

The computed tomographic appearance of the normal pituitary gland and pituitary microadenomas.

With the use of axial and coronal computed tomography (CT), the authors compared the density, contrast enhancement, and dimensions of normal pituitary glands and pituitary microadenomas. The normal gland appears homogeneous, nearly isodense with brain tissue, and it enhances uniformly. Its upper surface is concave downward or flat and its height 2-7 mm. The cavernous sinuses, the third, fourth, and sixth cranial nerves, the infundibulum, and the adjacent carotid arteries are well demonstrated by CT. Abnormal height and upward convexity of the gland are reliable signs of prolactinoma; abnormal density and enhancement are suggestive signs. CT findings in prolactin- and ACTH-secreting tumors may differ. CT is more sensitive and more specific than polytomography in the diagnosis of pituitary adenoma.

Adenoma