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Progestins of mink gestation: the effects of hypophysectomy.

Progesterone and 20alpha-hydroxypregn-4-ene-3-one (20alpha-ol) were determined from plasma samples taken weekly beginning 10 - 18 days before implantation in Pearl variety mink. Progesterone was low ( less than 8 ng/ml) until approximately five days prior to implantation when it increased and remained elevated (congruent to 30 ng/ml) through the early portion of postimplantation pregnancy. A subsequent decline was observed toward parturition. Mean concentrations of 20alpha-ol were relatively constant through gestation with a trend toward a greater proportion of progestin represented as 20alpha-ol during the preimplantation delay. Hypophysectomy prevented implantation, reduced progesterone levels and increased the concentration of 20alpha-ol relative to progesterone in plasma. These data suggest that prolactin (PRL) is a component of the luteotrophic complex in mink. Further, the corpus luteum of delay requires hypophyseal support for normal function.

20-alpha-Dihydroprogesterone↗

Lack of influence of hypophysectomy on estrogen-induced DNA synthesis in Leydig cells of BALB/c mice.

In mice of strains susceptible to Leydig cell tumor induction, treatment with estrogens induced a "spurt" of DNA synthesis within the first few days. This synthetic activity generally subsided, until areas of Leydig cell hyperplasia developed several months later. Autoradiographic and quantitative biochemical studies indicated that in BALB/c mice this initial DNA synthetic activity occurred in the absence of the hypophysis and apparently was the result of effects of estrogen directly on Leydig cells. Although hypophysectomy inhibited sperm maturation, [3H]thymidine incorporation into spermatogonia was reduced only slightly 2 weeks after surgery, as was the induced DNA spurt in the interstitial tissues.

Animals↗

The effects of food restriction and hypophysectomy on numbers of primordial follicles and concentrations of hormones in rats.

Three experiments were done to examine the effects of food restriction, beginning at 21 days of age, on loss of primordial follicles and on concentrations of gonadotropins and sex steroids in rats. In Experiment 1, food restriction (FR) from 21 to 51-55 days of age had no effect on number of primordial follicles, but increased the plasma concentration (p less than 0.05) of follicle stimulating hormone (FSH). (p less than 0.05). In Experiment 2, comparisons were made of groups of rats (1) fed ad libitum (AL) (2) hypophysectomized at 21 days of age and fed ad libitum (AL-HY), (3) food restriction from 21 to 52-58 days of age (FR), and (4) food restriction with twice-daily injections of follicular fluid (FR-FF). Hypophysectomy was the only treatment that decreased the loss of primordial follicles (p less than 0.001). Concentrations of FSH were decreased in AL-HY and increased in FR and FR-FF rats (144 +/- 13, 53 +/- 15, 275 +/- 30 and 359 +/- 56 ng/ml in AL, AL-HY, FR and FR-FF rats, respectively). Concentrations of luteinizing hormone (LH) were lower (p less than 0.05) in AL-HY, FR and FR-FF rats than in AL rats. In Experiment 3, AL and FR rats were unilaterally ovariectomized (ULO) at 30 days of age. Blood samples were taken 5 days prior to ULO, at ULO and at 12 h, 5 days, and 22-28 days after ULO.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Hypophysectomy of the cyclic mouse. I. Effects on folliculogenesis, oocyte growth, and follicle-stimulating hormone and human chorionic gonadotropin receptors.

The effects of hypophysectomy (HX) on folliculogenesis, oocyte growth, and ovarian FSH and LH receptors were examined by histology, topical autoradiography, and in vitro incubation of isolated follicles with [3H]thymidine. At random stages of the estrous cycle, mice were HX (Day 0), and they were killed from 0 to 20 days thereafter. Four days after HX, the number of preantral (stages 1-3) and antral (stages 4-5) follicles per ovary was reduced by 40% to 60% compared to Day 0 values, and stage 6 (large preovulatory) follicles had vanished. By Day 20 after HX, the numbers of follicles at stages 1, 2, and 4 were comparable to Day 4 values, whereas stage 3 and 5 follicles were still further diminished to 30% and 15% of Day 0 values, respectively. The number of atretic follicles from Days 0 to 20 after HX did not differ for follicles of stages 3-5, and stage 1 and 2 follicles were all healthy. However, oocyte growth was not coordinated with follicular growth after HX; the oocytes of stage 2-4 follicles were significantly larger than Day 0 oocytes. The enlarged oocytes appeared normal as judged by light and electron microscopy. DNA synthesis for stage 1-3 follicles declined significantly from Days 4 to 20 compared with Day 0 values, but did not change for stage 4 and 5 follicles, since atretic follicles at these stages were still labeled by [3H]thymidine and this was rare for Day 0 follicles. Topical autoradiography for [125I]-labeled FSH and hCG showed that follicular receptors for both hormones declined by Day 4 of HX and remained undetectable thereafter, except for trace amounts of [125I]-hCG binding in the interstitium. The decrease in follicular DNA synthesis and the greater diameter of oocytes in preantral follicles after HX suggest that longer transit times are required for one stage to progress to the next because of the anhormonal environment of the growing follicle. These results provide concrete evidence that pituitary gonadotropins are essential in the mouse for initiation, proliferation, and differentiation of all stages of growing follicles.

Animals↗

Sevoflurane increases lumbar cerebrospinal fluid pressure in normocapnic patients undergoing transsphenoidal hypophysectomy.

BACKGROUND: The data on the effect of sevoflurane on intracranial pressure in humans are still limited and inconclusive. The authors hypothesized that sevoflurane would increase intracranial pressure as compared to propofoL METHODS: In 20 patients with no evidence of mass effect undergoing transsphenoidal hypophysectomy, anesthesia was induced with intravenous fentanyl and propofol and maintained with 70% nitrous oxide in oxygen and a continuous propofol infusion, 100 microg x kg(-1) x min(-1). The authors assigned patients to two groups randomized to receive only continued propofol infusion (n = 10) or sevoflurane (n = 10) for 20 min. During the 20-min study period, each patient in the sevoflurane group received, in random order, two concentrations (0.5 times the minimum alveolar concentration [MAC] and 1.0 MAC end-tidal) of sevoflurane for 10 min each. The authors continuously monitored lumbar cerebrospinal fluid (CSF) pressure, blood pressure, heart rate, and anesthetic concentrations. RESULTS: Lumbar CSF pressure increased by 2+/-2 mmHg (mean+/-SD) with both 0.5 MAC and 1 MAC of sevoflurane. Cerebral perfusion pressure decreased by 11+/-5 mmHg with 0.5 MAC and by 15+/-4 mmHg with 1.0 MAC of sevoflurane. Systolic blood pressure decreased with both concentrations of sevoflurane. To maintain blood pressure within predetermined limits (within+/-20% of baseline value), phenylephrine was administered to 5 of 10 patients in the sevoflurane group (range = 50-300 microg) and no patients in the propofol group. Lumbar CSF pressure, cerebral perfusion pressure, and systolic blood pressure did not change in the propofol group. CONCLUSIONS: Sevoflurane, at 0.5 and 1.0 MAC, increases lumbar CSF pressure. The changes produced by 1.0 MAC sevoflurane did not differ from those observed in a previous study with 1.0 MAC isoflurane or desflurane.

Anesthetics, Inhalation↗

Transient induction of c-fos in rat magnocellular hypothalamic neurons after hypophysectomy.

Using immunofluorescence histochemistry, the paraventricular and supraoptic hypothalamic nuclei of normal control and hypophysectomized rats were studied in double labelling experiments with antibodies against the protein c-fos (Fos) and against vasopressin or oxytocin in order to characterize the activated neurons chemically. Normal controls showed no expression of Fos, whereas in hypophysectomized animals an intense induction of Fos-like immunoreactivity (-LI) was observed 12 h and 24 h post hypophysectomy but not beyond this survival time. Both vasopressinergic and oxytocinergic magnocellular neurons were labelled with Fos-LI. Thus Fos-LI can be induced in magnocellular hypothalamic neurons by injury, suggesting that this protein may be involved in adaptive mechanisms following axotomy.

Animals↗

Macronodular adrenal hyperplasia with hypothalamic-pituitary-adrenal suppression by ultra-high-dose dexamethasone: regression following hypophysectomy.

Cushing's syndrome associated with macronodular adrenal hyperplasia (MAH) may present with high-dose dexamethasone (dex) nonsuppressible hypercortisolemia. This has been interpreted as suggesting a primary adrenal disorder, leading to recommendations for curative adrenalectomy in these cases. The present case of MAH demonstrates high urinary and serum cortisol levels, sufficiently suppressed only by ultra-high-dose (32 mg/day X 2 day) dex, with parallel reduction of plasma adrenocorticotrophin noted as well. Subsequent clinical cure by transsphenoidal hypophysectomy and identification of a pituitary adenoma confirmed the secondary nature of adrenal cortical hypersecretion. The conceptual evolution of macronodules and altered feedback dynamics of the hypothalamo-pituitary-adrenal axis in MAH are briefly discussed.

Adrenal Gland Diseases↗

Exaggerated hemodynamic responses to nasal injection and awakening from anesthesia in a Cushingoid patient having transsphenoidal hypophysectomy.

A 51-year-old female patient, with an adrenocorticotrophic hormone-secreting pituitary tumor, was scheduled for transphenoidal hypophysectomy. She had a history of recent onset diabetes mellitus and a 2-year history of arterial hypertension. Despite ongoing medical therapy, preoperative blood pressure was 150-160/90-120 mm Hg. During general anesthesia, in response to perinasal infiltration with 10 ml of a solution containing lidocaine 200 mg and epinephrine 100 microg, blood pressure increased from 144/80 mm Hg to 317/175 over 3 minutes, as assessed by direct blood pressure monitoring. At the completion of the anesthetic, as the patient awakened and coughed and moved, blood pressure again increased dramatically, this time from 154/87 mm Hg to 285/170 over 3 minutes. Five months postoperatively, the patient's serum cortisol concentrations had normalized and her cuff blood pressure was 126/82, despite a reduction in her antihypertensive medications. The dramatic intraoperative blood pressure changes in this patient were attributed to the effects of hypercortisolemia on the normal physiologic responses to epinephrine and patient movement.

Administration, Intranasal↗

Hemodynamic responses to epinephrine-containing local anesthetic injection and to emergence from general anesthesia in transsphenoidal hypophysectomy patients.

Patients undergoing transsphenoidal pituitary surgery may experience hypertensive episodes during the intranasal injection of vasoconstrictor-supplemented local anesthetics or emergence from general anesthesia. The present research characterized the blood pressure responses during transsphenoidal surgery and tested the hypothesis that the underlying pituitary disease influences the incidence and magnitude of the blood pressure responses. The records of 100 patients were retrospectively reviewed. All had direct blood pressure measurements recorded using a computer-based anesthesia recording system. Mean age was 49 +/- 17 years (+/- SD) and 52% were male. Blood pressure increased by 60 +/- 37 mm Hg systolic and 23 +/- 22 mm Hg diastolic with intranasal injection and 42 +/- 24 mm Hg systolic and 23 +/- 16 mm Hg diastolic during emergence from general anesthesia. Systolic blood pressure increased by greater than 50% in 58% of patients following intranasal injection and in 33% of patients upon emergence from anesthesia. Blood pressure responses did not differ with respect to endocrinopathy type (Cushing's disease, acromegaly, or other pathology), gender, age, surgeon, history of prior transsphenoidal surgery, history of either hypertension or diabetes, or preoperative use of either beta-adrenergic or calcium channel-blocking drugs. There was poor correlation between the epinephrine dose injected (range 30-220 microg) and systolic blood pressure response (r = 0.24; r2 = 0.06; P = 0.031). Blood pressure increases were not associated with cardiac arrhythmias, persistent myocardial ischemia, or myocardial infarction. The authors conclude that in transsphenoidal hypophysectomy patients, large blood pressure increases are common with intranasal injection and upon awakening from general anesthesia. However, the authors were not able to find a variable that might enable the prediction of which patients are most likely to experience the most intense blood pressure elevations.

Acromegaly↗

Long term results of radical hypophysectomy for Cushing's disease.

Sixteen consecutive cases of Cushing's disease were treated by radical transphenoidal hypophysectomy. Surgical removal was not possible in two cases. Of the other 14, there was total clinical and biochemical remission of the disease in 13 and partial remission in one. Some form of replacement therapy has been necessary in 11 out of the 14 cases. During a long period of postoperative clinical and biochemical assessment extending over 5-14 years (average 8 years) there have been no recurrences.

17-Hydroxycorticosteroids↗

Molecular characterization of three rat liver serine-protease inhibitors affected by inflammation and hypophysectomy. Protein and mRNA analysis and cDNA cloning.

Rat hepatocytes have the potential to secrete three similar acidic glycoproteins, serine protease inhibitors 1, 2 and 3 (SPI-1, SPI-2, SPI-3), recognized by the same antibodies. They were synthesized as precursors of comparable sizes (45 kDa), which were post-translationally modified by N-glycosylation at three (SPI-3) or four (SPI-1 and SPI-2) sites. This appeared to account for the size difference of mature proteins. The mRNA sequences, derived from cDNA clones, displayed a high degree of similarity (70-90%), except the sequence of the antiprotease-reactive centers which were completely divergent. SPI-1 and SPI-2 mRNAs were of similar sizes (1.8 kb), and were smaller than that of SPI-3 (2.2 kb); the difference corresponded to a longer, 3'-end untranslated sequence. Production of SPI-1 and SPI-2, which was constitutive in the normal animal, could be abolished by hypophysectomy and was strongly decreased during acute inflammation. In contrast, production of SPI-3, which was barely detectable in normal rats, was transiently induced during inflammation.

Acute-Phase Proteins↗

The influence of LH and/or FSH on Leydig and Sertoli cell morphology after testicular involution in the Djungarian hamster, Phodopus sungorus, induced by hypophysectomy or short photoperiods.

In the Djungarian hamster, Phodopus sungorus, the morphological alterations of Sertoli and Leydig cells were investigated under the influence of gonadotropins (LH and/or FSH) after testicular regression induced either by hypophysectomy or photoinhibition. Stimulation with LH or LH/FSH lead to a redifferentiation of morphological features of Leydig cells such as nuclear structure, smooth endoplasmic reticulum and size of cell and nucleus area within 7 days of hormone treatment. Similarly, stimulation with FSH or LH/FSH caused redifferentiation of Sertoli cell nuclear structure, rough endoplasmic reticulum and nuclear size within 7 days. Incomplete restoration of Leydig and Sertoli cell morphology was observed under FSH and LH treatment respectively. In both Leydig and Sertoli cells combined LH and FSH application resulted in an increased response in respect to morphological redifferentiation, possibly indicating paracrine regulatory mechanisms. In all groups treated an intact blood-testis barrier (BTB) was reestablished after a minimum of 7 days, indicating that the existence of the blood-testis barrier is not dependent on specific gonadotropin supply but on the developmental stage of the seminiferous epithelium. Sham-operated animals showed increased cell and nucleus area of Leydig cells in comparison to photostimulated animals. After testicular involution as well as after LH or FSH treatment there were no significant morphological differences between hypophysectomized and photoinhibited animals in respect to the documented ultrastructural and morphometrical characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Histological studies on the effect of ACTH and flavin adenine dinucleotide on the rat adrenal cortex atrophied by hypophysectomy.

The present study describes the morphological changes in the adrenals of hypophysectomized rats injected 0.03 mg of ACTH and/or 10 mg of FAD intraperitoneally for 5 successive days starting 24 hrs after the operation. The administration of only FAD to intact or hypophysectomized rats showed no morphological change in the adrenal cortex. Simultaneous administration of FAD and ACTH to the hypophysectomized rats is more effective for preventing the atrophy induced than the administration of only ACTH. In these animals, similar morphological observations to those in the control, such as the increased nuclear volume, an increase of clear cells, diminuted numbers of lipid droplets and frequent occurrence of various types of granules, were obtained. FAD seems to be effective, through coexisting with ACTH, for preventing atrophy of the adrenals induced by hypophysectomy.

Adrenal Cortex↗

Enhancement of hypophysectomy-induced dopamine receptor hypersensitivity in male rats by chronic haloperidol administration.

It has been reported that hypophysectomy (HYPOX) would antagonize the development of a neuroleptic-induced dopamine receptor hypersensitivity, and suggested that the neuroleptic-induced dopamine receptor hypersensitivity may be mediated by the neuroleptic-induced hyperprolactinemia. Conversely, we and others have reported on the ability of HYPOX animals to develop a neuroleptic-induced dopamine receptor hypersensitivity. The present study was undertaken to define the possible role(s) of prolactin in the modulation of striatal dopamine receptor sensitivity. The data from these studies indicate: that HYPOX alone will result in the development of a striatal dopamine receptor hypersensitivity; that the HYPOX-induced dopamine receptor hypersensitivity could be increased by the chronic administration and withdrawal of haloperidol; that administration of prolactin to HYPOX rats would partially antagonize the development of the neuroleptic-induced dopamine receptor hypersensitivity; and that the administration of prolactin alone had minimal effects on the apomorphine-induced behavior or neurochemistry of the HYPOX animals. These results suggest that the neuroleptics do not require the presence of a pituitary secretion (specifically, prolactin) to induce a striatal dopamine receptor hypersensitivity; however, they do indicate that a pituitary secretion, perhaps prolactin, may have the ability to modulate striatal dopamine sensitivity.

Animals↗

Effects of adrenalectomy and hypophysectomy on enkephalin content of the rat hypothalamus.

1 Hypothalamic content of enkephalin in rats has been measured by bioassay against methionine-enkephalin on field-stimulated mouse vas deferens after acid extraction and purification using Amberlite XAD-2 resin.2 Surgical stress lowered hypothalamic enkephalin content initially but 6 days after operation the content was higher in sham-operated than in adrenalectomized animals.3 Corticosteroid replacement therapy showed that hypothalamic enkephalin content was not related directly to circulating corticosteroid levels and that it was increased by the stress of handling and injection.4 Hypothalamic enkephalin content of rats that had undergone hypophysectomy 11 days earlier did not differ from that of intact animals but surgical stress, which lowered content in intact rats and had no effect after adrenalectomy, produced a rise in content in these hypophysectomized animals.5 The ingestion of 0.9% saline, in place of water, by sham-adrenalectomized rats altered the effect of surgical stress on hypothalamic enkephalin content without affecting the resting levels.6 Of extracts from adrenalectomized rats, 10% contained a substance that behaved atypically on the mouse vas deferens, showing a slower onset and offset of action. The mol. wt. of the substance and sensitivity to naloxone reversal appeared to be similar to enkephalin, but it was resistant to carboxypeptidase-A and protease treatment.7 It is concluded that the enkephalin content of the hypothalamus is affected by activity in the hypothalamus-pituitary-adrenal system but that it is not related in a simple manner to the levels of corticotrophin releasing hormone, corticotrophin or corticosteroids.

Adrenal Cortex Hormones↗

Transsphenoidal hypophysectomy in the dog. A new technique.

A technique for localizing the canine hypophysis regardless of the shape or size of a dog's skull was evaluated. Using known anatomic landmarks, the approximate location of the hypophysis was estimated, and three small self-threading screws were placed as radiographic markers in the exposed sphenoid bone. A cranial sinus venogram was performed and the hypophysis was outlined by the contrast-filled cavernous sinus. A circular ostectomy was centered over the hypophysis, using the previously placed screws as reference points. The technique was evaluated in eight dogs in a nonsurvival procedure. In seven dogs, hypophysectomy was complete and the ostectomy sites were centered precisely over the hypophysis.

Animals↗

Enhanced effect of haloperidol and apomorphine after hypophysectomy: pharmacokinetic considerations.

The behavioural effects of both apomorphine (stereotypies) and haloperidol (catalepsy and reversal of stereotypies) were significantly enhanced in hypophysectomized rats compared with sham-operated rats. Both the efficacy and duration of action were increased Hypophysectomized animals had significantly greater brain haloperidol concentrations than did sham-operated animals. The data suggest that changes in brain drug concentrations following hypophysectomy at least partially explain the behavioural alterations seen in this test situation.

Animals↗

Diuresis from atrial receptors after hypophysectomy and local ablation with no changes in plasma vasopressin.

Stimulation of the left atrial receptors in dogs anaesthetized with chloralose results in a reflex diuresis and natriuresis. The efferent limb of this reflex is though to have at least three components: nervous, haemodynamic and humoral. The present study was designed to investigate the humoral component in dogs anaesthetized with chloralose; to determine whether a humoral agent, other than vasopressin, might be causative in this reflex diuresis. The nervous and haemodynamic components were prevented by pharmacological denervation. Any possible contribution to the diuresis by a decrease in the plasma concentration of vasopressin was prevented by the removal of the pituitary gland. In animals in which a spontaneous diuresis followed hypophysectomy, an infusion of arginine vasopressin sufficient to maintain urine flow in the normal range for these dogs anaesthetized with chloralose was given. Distension of small balloons at the pulmonary vein-atrial junctions and in the left atrial appendage discretely to stimulate the atrial receptors in eleven dogs anaesthetized with chloralose resulted in a significant diuresis. It was concluded that a blood-borne agent other than vasopressin was responsible for the observed diuresis. At the moment it is not known whether vasopressin or the diuretic agent, or both, are involved in the diuresis accompanying the stimulation of atrial receptors.

Animals↗