Heterotopic Pituitaries Research Articles

Hypothyroidism Increases Substance P Concentrations in the Heterotopic Anterior Pituitary*

The regulatory effects of thyroid hormone on adenohypophysial substance P (SP) were studied in heterotopically implanted anterior pituitaries. Three or four anterior pituitaries from 21-day-old rat pups were implanted under the renal capsule in 175- to 200-g adult rats. The donor and recipient animals were sex matched. One week after implantation, animals were thyroidectomized or sham operated. A separate group of animals received daily T4 treatment (1.5 g/100 g, ip). After 2 weeks, the native and heterotopic pituitaries were assayed for SP, TSH, PRL, and LH. Thyroidectomy resulted in a 3- to 10-fold increase in the SP concentration in both the heterotopic and native pituitaries compared to euthyroid values. T4 treatment suppressed the SP levels in the heterotopic pituitaries of the thyroidectomized rats. In contrast to the reduction of TSH concentrations in native pituitaries in thyroidectomized animals vs. controls, TSH concentrations in the heterotopic pituitaries of thyroidectomized rats were approximately 10 times greater than those in euthyroid animals. PRL concentrations were unaffected by hypothyroidism in native and heterotopic pituitaries. Thyroidectomy resulted in a decrease in LH concentrations in the native anterior pituitary, without affecting LH concentrations in the implanted pituitary. These findings indicate that a direct link from the hypothalamus to the anterior pituitary is not required for the pituitary SP response to hypothyroidism.

In vitro TSH and PRL secretion from eutopic and heterotopic rat pituitaries: effects of hypothyroidism.

Five adenohypophyses from donors of the same strain, age, and sex were transplanted under the renal capsule of young adult female rats. At least 3 wk later, enzymatically dispersed cells from eutopic or heterotopic adenohypophyses from the same rat were perifused in vitro in a small chamber. Thyrotropin (TSH) and prolactin (PRL) secretion per 10(6) cells were significantly less from heterotopic than from eutopic cells under all conditions. In cells from euthyroid animals, TRH induced TSH secretion only in the eutopic cells but induced PRL secretion in both eutopic and heterotopic cells. Hypothyroidism increased TRH-induced TSH secretion and content in the cell lysate in both eutopic and heterotopic cells but increased TRH-induced PRL secretion only in the eutopic cells. The increase in TSH secretion induced by hypothyroidism in the heterotopic cells was of borderline statistical significance. The inability of TRH to induce TSH secretion in heterotopic pituitary cells from euthyroid rats may be due to a lower set point for thyroid hormone inhibition of TSH secretion in the heterotopic thyrotrophs. Heterotopic pituitary TSH secretion is probably suppressed by the normal plasma thyroid hormone concentration maintained by the eutopic pituitary and may be stimulated by TRH only in the presence of a subnormal plasma thyroid hormone concentration.

Evidence that regulation of thyrotropin secretion by the heterotopic pituitary is independent of endogenous thyrotropin-releasing hormone from any source.

AbstractEqual quantities of rabbit antithyrotropin-releasing hormone serum (TRH-AS) or normal rabbit serum (NRS) were administered to rats made hypothyroid by chronic feeding of propylthiouracil. TRH-AS produced a 37% decrease in plasma thyrotropin (TSH) (P < 0.01) in intact rats, but caused no significant decrease in plasma TSH concentration in hypophysectomized rats bearing three heterotopic pituitary transplants under the kidney capsule. NRS had no significant effect on plasma TSH in either group. This supports other data indicating that secretion of TSH and prolactin by heterotopic pituitaries is not under significant control by TRH in the general circulation.

Evidence that thyrotropin and prolactin are not secreted by the posterior pituitary of the rat.

After eutopic hypophysectomy of the host, transplants under the renal capsule of three whole pituitaries or of the adenohypophysis alone were capable of maintaining plasma PRL concentration equal to or greater than that of intact controls. The basal plasma TSH levels in rats with these types of heterotopic pituitaries was below that of intact controls but was significantly increased by TRH or chronic antithyroid treatment. Rats with posterior pituitary (intermediate and neural lobe) heterotopic transplants were incapable, under any conditions tested, of raising the plasma PRL or TSH concentration above that seen in hypophysectomized controls without pituitary transplants. In a further experiment, selective extirpation of the anterior or posterior lobe of the eutopic pituitary was performed. Plasma concentrations of TSH and PRL in rats with anterior lobectomy were not significantly different from those of hypophysectomized controls but were significantly higher than those of hypophysectomized controls in rats with posterior lobectomy. These data indicate that only the adenohypophysis secretes physiologically significant quantitites of these two hormones. (Endocrinology 108: 382, 1981)

Release of Growth Hormone by TRH in Intact Rats or in Intact or Hypophysectomized Rats bearing a Heterotopic Pituitary

SummaryThyrotropin-releasing hormone (TRH) was administered iv using ure-thane anesthesia to either intact female and male controls or intact (IT) or hypophysec-tomized (HT) rats of both sexes bearing an anterior pituitary (AP) graft under the kidney capsule. TRH at all the doses used (0.15, 0.6, and 1.2 μg) elicited a clear GH rise in both IT and HT rats, while only at the highest does (1.2 μg) was it effective in intact controls. Qualitative and quantitative electron microscopic studies performed on the in situ and ectopic pituitaries from IT female rats demonstrated that TRH stimulated exocytosis from the ectopic pituitary at all doses used, whereas only the highest TRH dose was capable of increasing the frequency of exocytosis from the pituitary in situ. The similar responsiveness to TRH of the ectopic pituitary irrespective of the presence of an in situ AP, rules out the possibility that peripheral hormonal factors (e.g., lack of estrogens or thyroid hormones) may play a crucial role in the preferent...

The response of the heterotopic pituitary to thyrotropin releasing hormone (TRH).

The ability of pituitary glands grafted beneath thekidney capsule to mediate a discharge of ¹²⁵I from the thyroid gland in response to i. v. injections of TRH was evaluated by blood ¹²⁵I measurements. The minimum effective dose (3.3 ng TRH/rat) was less than that found for rats with intact pituitaries under the same conditions (10 ng TRH/rat). At higher dose levels the intact rats gave bigger responses than did rats with heterotopic pituitaries. The heterotopic pituitary retains its sensitivity to the releasing action of TRH but the magnitude of its responses is limited by the small amount of TSH available for release.

The effect of surgical isolation of the basal hypothalamus on the nycthemeral rhythm of plasma corticosterone concentration in rats with heterotonic pituitaries.

The effect of total hypothalamic deafferentation on the nycthemeral rhythm of plasma corticosterone concentration was studied in rats with in situ or heterotopically transplanted pituitaries. Ten pituitaries from 21-day-old donors were transplanted in 120-g male recipients. Hypophysectomy was performed four weeks following transplantation. One week later the basal hypothalamus was surgically isolated. Post-transplantation AM and PM levels of plasma corticosterone were not different from those of unoperated controls. Following hypophysectomy there was a reduction in the amplitude of the plasma corticosterone rhythm. Surgical isolation of the basal hypothalamus, in both the heterotopic and in situ preparations, abolished the AM-PM differences of plasma corticosterone concentration. It is concluded that the nycthemeral rhythm of ACTH secretion of both in situ and heterotopic pituitaries requires the integrity of neural connections between the basal hypothalamus and the rest of the brain. (Endocrinology 91: 8...

Relation of the Mass of Heterotopic Pituitary Tissue to Its Ability To Secrete ACTH and TSH in Response to Amino-glutethimide

One, 2, 4, 8 or 16 pituitaries from immature donors were transplanted under the kidney capsule of young adult male hosts of the same Sprague-Dawley-derived strain. Four weeks later the rats were hypophysectomized; 2 weeks later half of each group was fed a diet containing 0.4% Elipten for 14 or 19 days. The remaining rats were continued with a Purina diet. In the Purina-fed animals, relative thyroid size was not different in any transplanted group from that of intact controls; relative adrenal size was significantly smaller in rats with only a few heterotopic pituitaries than in intact controls, but increased proportionately to the mass of ectopic pituitary tissue. Elipten induced marked adrenal and thyroid hypertrophy in the intact controls. It also induced significant relativeadrenal hypertrophy in all groups of transplanted rats. In contrast, relative thyroid hypertrophy was produced in transplanted animals only if 4 or more pituitaries were present. There was a significant positive correlation of rela...

Studies on the glucocorticoid feedback control of ACTH secretion.

Implants of cortisol acetate in the median eminence of intact rats depressed all measures of adrenocortical function compared with rats which had received cholesterol in the median eminence or an equal amount of cortisol acetate implanted in the cerebral cortex. Lesions in the median eminence of intact rats also depressed adrenocortical function. In contrast, neither implants of cortisol acetate nor lesions in the median eminence depressed adrenocortical function in hypophysectomized rats bearing 10 heterotopic pituitaries (H-T). A large dose of dexamethasone (100 Mg/100 g) given systemically suppressed adrenocortical function in both intact and H-T rats. Additionally, implants of cortisol acetate in the median eminence were followed in 2 weeks by adrenal atrophy in intact rats, whereas the adrenal size of H-T rats was unaffected. These findings suggest that the median eminence does not play an important role in feedback control of heterotopic pituitary ACTH secretion. The median eminence may be of import...

Diurnal variation of adrenocortical function in hypophysectomized rats with multiple heterotopic pituitary homografts.

WE have shown that hypophysectomized male rats bearing ten heterotopic, homografted pituitaries under the renal capsules have nearly normal adrenal weight and considerable, though subnormal, adrenal corticosterone production1. Because adrenal weight and production of corticosterone was markedly reduced in hypophysectomized rats without pituitary homografts, we concluded that the heterotopic pituitary has adrenal-maintaining activity presumably by means of the secretion of ACTH. Furthermore, because many investigators have shown that a single heterotopic pituitary exhibits only very slight adrenal-maintaining activity2–4, we concluded that multiple heterotopic pituitaries maintain adrenal weight by virtue of their collective secretion of individually small amounts of ACTH. The present communication deals with studies of diurnal variation in the function of the cortex of the adrenal glands in rats with pituitary homografts and provides evidence that direct connexion between the brain and pituitary is not essential for the rhythmic activity of the pituitary-adrenocortical axis.

Brain-Dependent TSH Secretion from Heterotopic Pituitaries

Brain-Dependent TSH Secretion from Heterotopic Pituitaries

Brain-dependent ACTH secretion from multiple heterotopic pituitaries.

SummaryHypophysectomized rats with multiple heterotopic pituitaries have nearly normal adrenal weight and significant, though subnormal, corticosterone secretion. Removal of the entire forebrain, but not decortication, in these animals reduced corticosterone secretion nearly to values found in hypophysectomized control animals. These results indicate that heterotopic pituitary ACTH secretion is dependent on some subcortical portion of the forebrain.

Evidence for ACTH secretion and ACTH suppressibility in hypophysectomized rats with multiple heterotopic pituitaries.

Previous studies have shown poor maintenance of adrenal weight and adrenocortical function when 1–4 pituitaries were heterotopically transplanted in hypophysectomized rats. In the present studies, hypophysectomized male rats bearing 10 heterotopic pituitary homotransplants maintained nearly normal adrenal weight. Adrenocortical secretion of corticosterone, aorta plasma corticosterone and adrenal corticosterone concentration were significantly higher than in hypophysectomized controls. These findings suggest that the amount of ACTH secreted in these animals is a function of the number of pituitaries transplanted. Suppression of corticosterone secretion by dexamethasone was similar in both transplanted and intact animals, indicating that contiguity of the pituitary with the hypothalamic median eminence is not essential for the suppression of ACTH secretion by corticosteroids. (Endocrinology 78: 533, 1966)

Corticosterone in mouse adrenal in relation to sex and heterotopic pituitary isografting.

In two populations of mice, one inbred (C, Bag albino), the other hybrid, adrenal ‘corticosterone’ levels determined at time of peak physiologic secretion differed consistently between the two sexes. The female glands, heavier than those of males, had the higher content and concentration of ‘corticosterone.’ In female C and D8 (Dilute Brown, subline 8) mice, adrenal ‘corticosterone’ content is further elevated during a period from about 64 to about 180 days after pituitary isografting; i.e. many months prior to the appearance of breast cancers, induced or enhanced in these stocks by the heterotopic pituitary.