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Cell kinetics in the epidermis of the toad Bufo bufo bufo (L.) after partial hypophysectomy followed by corticotrophin treatment (an autoradiographic study).

1. Cell kinetic parameters in the epidermis of partially hypophysectomized, ACTH-treated toads whose moulting frequency was increased threefold were studied using labelled thymidine and the autoradiographic technique. 2. The labelling index, length of S-phase and cycle time of stratum germinativum cells changed slowly as a function of the number of ACTH injections, and so did the migration of cells from stratum germinativum to stratum corneum. 3. A cell production in stratum germinativum of normal toads in excess of cell loss, as demonstrated by Levi & Nielsen (1982) should make it possible to maintain a status quo over a limited period of time following ablation of pars distalis and ACTH treatment.

Adrenocorticotropic Hormone↗

Hypophysectomy does not disturb the sleep-waking cycle in the cat.

The ablation of the hypophysis does not disturb the basic waking-sleep cycle. Further, this intervention fails to modify the recovery of sleep after instrumental paradoxical sleep deprivation as well as after injection of 5-hydroxytryptophan in parachlorophenylalanine-pretreated insomniac cats. These results demonstrate that the hypophysis does not play a significant role in sleep mechanisms. We discuss these data in view of a possible regulation of the sleep-waking cycle by hypothalamo-hypophyseal hormones.

Animals↗

Fetal hypophysectomy causes a decrease in preadipocyte growth and insulin like growth factor-1 in pigs.

Fetal pigs in one uterine horn of each of five gilts were hypophysectomized (HX) in utero by electrical cauterization at 72-74 days of gestation and sera collected at 110 days of gestation. Sera from HX fetuses had lower levels of insulin-like growth factor-1 compared to control littermates (P less than .05). Sera were tested for their effects on primary cultures of stromal-vascular cells from adipose tissue. The soluble protein concentration/dish was lower when pig cells were cultured in sera from HX fetuses compared to sera from control fetuses (P less than .01). Sera from HX fetuses inadequately supported growth of stromal-vascular cells so subsequent experiments utilized pooled sera from normal and HX adult pigs. Sera from HX and control fetuses were mixed with sera from the two adult pools and tested for incorporation of tritiated thymidine into rat preadipocytes and the appearance of adipocytes (determined histochemically) in pig stromal-vascular cultures. In cultures fed sera from HX fetuses there was a lower (P less than .05) number of pig fat cells/culture and a lower level (P less than .06) of preadipocyte proliferation in rat cell cultures when compared to control fetal sera. Fetal pig serum contains factors (adipogenic) which promote the proliferation and differentiation of adipocytes in culture. Serum from HX fetuses has a lower level of adipogenic factors.

Adipose Tissue↗

Hypophysectomy and growth hormone replacement effects on multiple immune responses in rats.

Male Fischer 344 rats were hypophysectomized at 8 weeks of age. At 10 weeks of age, one group of these animals was treated with 40 micrograms of bovine somatotropin given daily sc for 13 days. A third group was sham-operated and injected daily with saline. All animals were sacrificed on Day 14 and multiple immune responses were assessed in each rat. Immune responses assayed included specific antibody production and delayed-type hypersensitivity (DTH) reactions to antigen, natural killer (NK) cell cytotoxicity, and production of interleukin 2 (IL2). Body and lymphoid organ weights, hematologic parameters, and spleen cell numbers were also recorded. Hypophysectomized (Hx) rats had reduced antibody synthesis, DTH reactions, NK cytotoxicity, IL2 (or IL4) production, body and organ weights, rbc counts, packed cell volumes, and hematocrits compared to sham-operated controls. White blood cell counts were elevated. Treatment of Hx animals with GH restored antibody and IL2 production and thymic weights and partially restored DTH reactions. These data indicate the pituitary is important in maintaining normal immune functions, and part of this effect may be via production of GH. It is postulated that GH may act through stimulation of IL2 (or IL4).

Animals↗

Pituitary control of cholesterol metabolism in normal and LDL receptor knock-out mice: effects of hypophysectomy and growth hormone treatment.

The pituitary is important in the control of lipid metabolism and studies of hypophysectomized (Hx) rats have shown strong effects of growth hormone (GH) on bile acid synthesis, hepatic LDL receptor (LDLR) expression and on the sensitivity to dietary cholesterol. It is unclear if mice may be used in such studies. The aim of the current study was to evaluate if Hx mice may be used to further explore how GH modulates cholesterol and bile acid metabolism, and to define the importance of the LDLR in this regulation by studying LDLR-deficient mice (LDLRko). Experiments on three mouse strains showed that, following Hx, HDL were reduced and LDL increased. Cholesterol/fat feeding of Hx mice increased serum cholesterol levels 2- to 3-fold. Serum triglycerides were reduced 50% in Hx mice; a further 30% reduction was seen after dietary cholesterol/fat. A serum marker for CYP7A1-mediated bile acid synthesis (C4) increased 2-fold in intact mice on cholesterol/fat diet. In Hx mice C4 levels were reduced by 50% as compared to intact controls, but were unexpectedly increased to levels seen in normal mice upon cholesterol/fat feeding. Hx of LDLRko mice moderately increased LDL-cholesterol and reduced triglycerides and GH treatment attenuated these effects; serum C4 levels were increased by GH treatment in all groups. In conclusion, mice can be used to explore the role of the pituitary in lipid metabolism. CYP7A1 is generally reduced in Hx mice but has a normal stimulatory response following dietary cholesterol suggesting that faulty regulation of CYP7A1 is not important for the reduced resistance to dietary cholesterol in Hx mice. Further, the LDLR is only to a minor part involved in the pituitary regulation of serum cholesterol in mice.

Animals↗

Hypophysectomy does not block sensitization to the dopamine agonist quinpirole or its modulation by the MAOI clorgyline.

Repeated administration of the dopamine agonist quinpirole induces behavioral sensitization in rats that is characterized by a four- to eight-fold increase in the amount of locomotion compared to an acute dose of quinpirole, in the absence of any increases in mouthing behavior. The monoamine oxidase (MAO) inhibitor, clorgyline, switches behavioral sensitization to quinpirole from that of locomotion to self-directed mouthing. The mechanism by which clorgyline produces this switch in behavioral sensitization is unknown, but is independent of the known effects of clorgyline, namely, inhibition of MAO, inhibition of striatal dopamine uptake, or stimulation of sigma and I(2) receptors. Because clorgyline also inhibits hypothalamo-pituitary-adrenal (HPA) axis function, and increased HPA activity facilitates the behavioral effects of psychostimulant drugs, the effects of clorgyline on quinpirole sensitization are possibly due to an inhibition of HPA function. Therefore, the present study examined whether HPA activity is required for sensitization to quinpirole, and whether clorgyline exerts its effects on quinpirole sensitization via inhibition of HPA function. Control and hypophysectomized rats were administered clorgyline (1 mg/kg, s.c.) or vehicle 90 min before each injection of quinpirole (0.5 mg/kg x 8, twice weekly) or saline. To assess the level of sensitization reached by control and hypophysectomized rats, test injections of quinpirole (0.0, 0.07, and 0.2 mg/kg) were administered. Chronic quinpirole administration produced equivalent levels of locomotor sensitization in control and hypophysectomized rats. Clorgyline was equally effective in blocking the development of locomotor sensitization in control and hypophysectomized rats, and in sensitizing self-directed mouthing. The present study suggests that (1). HPA function is not necessary for the development of quinpirole sensitization and, (2). clorgyline does not produce its effects on behavioral sensitization to quinpirole via an inhibition of HPA activity. Moreover, the observation that quinpirole sensitization develops normally in the absence of any pituitary endocrine function suggests that pituitary-gonadal and pituitary-thyroid axes activity are also not necessary for quinpirole sensitization to occur.

Animals↗