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.     

Functional and morphological effects of hypophysectomy and androgen replacement in the rabbit epididymis

Summary The fertilizing ability of spermatozoa from the distal corpus epididymidis of 55 male rabbits of proven fertility has been determined after artificial insemination 1, 2, 3, 5, 7, and 11 days after hypophysectomy. A significant decrease in fertility was noted 3, 5, and 7 days after hypophysectomy. Testosterone propionate (2 mg/kg/day) given for 7 days to hypophysectomized rabbits maintained the fertilizing ability of spermatozoa from the corpus epididymidis when injections were started from the day of hypophysectomy or delayed by a week. The effect of hypophysectomy on the histological features of the epididymal epithelium were studied with light and electron microscopy. Regressive changes were observed: reduction in size of the stereocilia border and the endoplasmic reticulum 3 days after hypophysectomy followed by a decrease in tubular diameter and cell height, a reduction in size of the Golgi apparatus and an increase in number of lysosome-like figures and a vacuolization of the epithelium.These results are discussed in relation to the physiological requirements for sperm maturation.     

Les tissus élaborateurs d'hormones stéroïdes chez les amphibiens urodèles

Résumé Les cellules du tissu glandulaire du testicule et de la glande interrénale de pleurodèle montrent les caractères généralement observés dans les cellules stéroïdogènes. Des différences existent entre les deux tissus. Le reticulum endoplasmique du tissu glandulaire est très développé et présent dans toutes les cellules qui sont d'aspect homogène. Au contraire, le tissu interrénal montre deux aspects cellulaires différents. Le premier se caractérise par un reticulum endoplasmique lisse relativement peu développé par rapport au tissu glandulaire, par des mitochondries petites et nombreuses, enfin par des liposomes denses et petits. Le deuxième aspect au contraire, se distingue par le petit nombre de mitochondries souvent géantes et à crêtes plus fréquemment organisées en faisceaux, par des liposomes nombreux de grandes dimensions et peu denses aux électrons.Le tissu glandulaire est très peu touché par l'hypophysectomie. Le reticulum persiste plusieurs mois comme d'ailleurs l'activité 5-3 -hydroxystéroïde deshydrogénase. Dans le tissu interrénal, la proportion des cellules d'aspects différents varie au profit des cellules à lipides abondants et à grandes mitochondries. L'activité 5-3 -hydroxystéroïde deshydrogénase est longtemps décelable.Le rôle du reticulum endoplasmique du tissu glandulaire est discuté en fonction des observations réalisées dans d'autres cellules stéroïdogènes à reticulum abondant. La signification des deux aspects cellulaires observés dans l'interrénale est discutée en relation avec les résultats expérimentaux obtenus en particulier chez le rat.Cette étude révèle que les critères d'activité d'une cellule stéroïdogène sont délicats à établir et doivent être différents d'un tissu à l'autre.

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Tissues secreting steroid hormones in urodele amphibians

Summary The fine structure of testis glandular tissue and interrenal gland cells of Pleurodeles shows the general features observed in other steroïdogenic cells. Certain differences exist between the two tissues. The agranular endoplasmic reticulum of the glandular tissue cells is well developed and present in all cells of similar appearance. On the contrary, the interrenal tissue cells show two different features. The first is characterised by a poorly developed smooth endoplasmic reticulum, compared with that of the glandular tissue, by small and numerous mitochondria, and finally by small electron dense lipid droplets. The second feature is the small number of mitochondria often giant and with fascicles of straight tubular cristae and numerous large lipid droplets of low electron density.The effect of hypophysectomy on the glandular tissue cells seem very slight. The endoplasmic reticulum and the 5-3 -hydroxysteroid dehydrogenase activity persists for several months. In the interrenal tissue, the proportions of the two different cellular features are modified. Cells rich in lipids and with large mitochondria are more abundant. It is possible to demonstrate a 5-3 -hydroxysteroid dehydrogenase activity for a long time after hypophysectomy. The functional significance of the agranular endoplasmic reticulum is discussed in relation to some other observations on different steroidogenic cells with a well developed agranular endoplasmic reticulum. The significance of the two cellular features observed in the interrenal gland is discussed in connection with experimental data obtained in the frog and the rat.This study shows that it is difficult to define criteria of cellular activity, which probably differ from one tissue to another.

Equipe de Recherche associée au C. N. R. S. Cytologie Ultrastructurale n 129.     

Effects of epidermal growth factor on deoxyribonucleic acid synthesis and stomach weight in hypophysectomized adult mice

Epidermal growth factor (EGF) or saline was administered intraperitonally to hypophysectomized adult male CD2F₁ mice or intact controls at 0700 hr. Subgroups of mice were killed at 4, 8, or 12 hr after injection. EGF was shown to stimulate [³H]TdR incorporation into DNA into several organs as previously reported. The response to EGF was found to be enhanced in both hypophysectomized and fasted mice. Differences in [³H]TdR incorporation into DNA, corneal epithelium mitotic index, RNA in pancreas and kidney of hypophysectomized and intact mice are reported. EGF was shown to result in stomach enlargement due to increased luminal contents in both hypophysectomized and intact mice.     

Effect of hypophysectomy and growth hormone replacement on hypothalamic GHRH

Long-term (7 and 14 days) hypophysectomy resulted in a striking decrease in growth hormone releasing hormone-like immunoreactivity (GHRH-LI) in the median eminence (ME) of adult male rats, evaluated by both radioimmunoassay and immunohistochemistry. Treatment with human GH (125 μg/rat, twice daily IP for 14 days) prevented, though partially, depletion of GHRH-LI from the ME, as assessed by both methods. These results demonstrate that circulating GH levels regulate the function of GHRH-producing structures, via a feedback mechanism.     

Results of repeated transsphenoidal surgery in Cushing's disease. Long-term follow-up

ObjectiveTranssphenoidal surgery (TSS) is the treatment of choice for Cushing's disease (CD). However, the best treatment option when hypercortisolism persists or recurs remains unknown. The aim of this study was to analyze the short and long-term outcome of repeat TSS in this situation and to search for response predictors.Patients and methodsData from 26 patients with persistent (n = 11) or recurrent (n = 15) hypercortisolism who underwent repeat surgery by a single neurosurgeon between 1982 and 2009 were retrospectively analyzed. Remission was defined as normalization of urinary free cortisol (UFC) levels, and recurrence as presence of elevated UFC levels after having achieved remission. The following potential outcome predictors were analyzed: adrenal status (persistence or recurrence) after initial TSS, tumor identification in imaging tests, degree of hypercortisolism before repeat TSS, same/different surgeon in both TSS, and time to repeat surgery.ResultsImmediate postoperative remission was achieved in 12 patients (46.2%). Five of the 10 patients with available follow-up data relapsed after surgery (median time to recurrence, 13 months). New hormone deficiencies were seen in seven patients (37%), and two patients had cerebrospinal fluid leakage. No other major complications occurred. None of the preoperative factors analyzed was predictive of surgical outcome.ConclusionsWhen compared to initial surgery, repeat TSS for CD is associated to a lower remission rate and a higher risk of recurrence and complications. Further studies are needed to define outcome predictors.     

Behavioral support for an ACTH receptor in the CNS

In this report we present a series of experiments which have led us to support the notion of the presence of an ACTH receptor in the CNS. A short intense heat-stress (hot-plate) applied to the paws of rats will temporarily reduce activity. During the course of experimentation we were able to eliminate a number of logical mediators. Neither adrenalectomy, adrenal-medullectomy, naloxone administration, nor alpha-MSH-(1-12) were able to affect the observed akinesia. Hypophysectomy, however, was able to abolish or mask the behavior and the reduction in activity could be reinstated by the administration of ACTH-(4-10) to hypophysectomised rats. These data support the notion that a short intense stressor can release ACTH and that this ACTH can be responsible for mediating the short term reduction in activity. In addition, the fact that ACTH-(4-10) has only minimal steroidogenic properties and was able to reinstate the behavior led us to speculate that these effects were of central origin. Furthermore, since naloxone was not capable of altering the behavior, the suggestion is that ACTH in this paradigm acted at a receptor site apart from the naloxone sensitive receptor. This site may in fact be an ACTH specific receptor.     

Hormonal regulation of sulfated glycoprotein-1 synthesis by nonciliated cells of the efferent ducts of adult rats

The objective of this study was to define the factors regulating the endogenous production of sulfated glycoprotein-1 (SGP-1) in nonciliated cells of the efferent ducts. To this end we examined five different groups of animals undergoing the following experimental procedures: (1) hypophysectomized animals at 7, 14, and 28 days, (2) 7-day hypophysectomized rats receiving testosterone implants given at various time intervals thereafter, (3) castration at various time intervals up to 7 days, (4) 7-day castrated rats receiving testosterone implants at various time intervals thereafter, and (5) castrated rats given testosterone implants immediately after castration and sacrificed at different time intervals thereafter. Efferent ducts were fixed by perfusion with 4% paraformaldehyde and 0.5% glutaraldehyde in phosphate buffer for quantitative immunocytochemical analysis at the level of the electron microscope. For each experimental condition and their controls, the number of gold particles/μm² within the endosomal and lysosomal compartments was calculated taking into account the changes in both the volume of the cell and organelles being quantified and expressed as labeling content. The results revealed that hypophysectomy (up to 4 weeks) caused a marked significant decrease in the SGP-1 labeling content of the endosomal and lysosomal compartments. The labeling content of the lysosomal compartment of efferent ducts from rats castrated for up to 1 week did not change significantly. However, there was a significant decrease in the labeling content of endosomes. This decrease is due to SGP-1, which is secreted by Sertoli cells, not being available for uptake in the efferent aucts. These results suggested that testosterone is not required for maintaining the high labeling content of SGP-1 within lysosomes of nonciliated cells, but that a pituitary factor appears to be needed. The administration of testosterone at different intervals to 7-day castrated animals resulted in a significant decrease of lysosomal SGP-1, suggesting that testosterone under these experimental conditions inhibits the production of a pituitary factor that maintains the high labeling content of SGP-1 within lysosomes of the nonciliated cells. Testosterone administered to 7-day hypophysectomized animals over a 24-hr period had no effect on the labeling content of SGP-1 within lysosomes. However, the administration of testosterone to animals immediately following castration showed no differences in the labeling content of SGP-1 within compared to controls. Together these results suggest that the labeling content of SGP-1 within lysosomes of nonciliated cells of the efferent ducts is not dependent on luminal or circulating androgens, nor is it dependent on a testicular factor entering the lumen of the ducts. It does appear, however, that SGP-1 synthesis and targeting to secondary lysosomes is dependent on a pituitary factor that may have a direct or an indirect effect on the nonciliated cells. © 1995 Wiley-Liss, Inc.     

Effect of cycloheximide on the fine structure of corpus luteum in intact and hypophysectomized rats

Summary In rats, one large intravenous dose of cycloheximide leads to extensive development of two types of membrane-formations in the cells of corpora lutea, within two hours. Both the laminated dense bodies (concentric layers of smooth membranes showing high electron density) and the tubular aggregates (tightly packed smooth tubules with diameter smaller than usual) exhibited obvious connections with endoplasmic reticulum membranes. The reorganization of tubular aggregates gave rise to crystalloids showing hexagonal symmetry. The crystalloids, being obviously unstable, were transformed into smooth fingerprints (concentric arrays of paired agranular membranes showing the same density as endoplasmic reticulum membranes). Hypophysectomy, performed 24 hours previously, moderated but did not totally abolish the development of membranous configurations. The described effect of cycloheximide is considered to represent cellular injury, probably due to membrane-denaturation.This work was supported in part by the Medical Research Council of Canada (Block Term Grant MT-1829), the Ministère des Affaires Sociales, Quebec, and Succession J.A. DeSève. The authors thank the Upjohn Company, Kalamazoo, Michigan, U.S.A., for the cycloheximide used in these experiments.Fellow of the Medical Research Council of Canada.