Evidence for Renotropic Activity in Ovine Pituitaries*

Nicholson, Wendell E.; Barton, R. N.; Puett, David; Orth, David N.; Liddle, Grant W.

doi:10.1210/endo-105-1-16

Cited by 18 publications

(8 citation statements)

References 13 publications

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“…Earlier we showed that, when assayed at the same levels found in the crude renotropic fraction, combinations of these hormones were unable to stimulate renal growth (5). Thus, the renotropic activity of our fraction does not appear to reside in GH or ACTH.…”

Section: Discussionmentioning

confidence: 53%

“…This renotropic activity was also observed in hypophysectomized castrated rats, demonstrating that the activity was not mediated solely by androgens which are known to stimulate renal growth in rats (6). In addition, human choriogonadotropin (hCG) was ineffective in restoring the renal weight of hypophysectomized castrated rats (5).…”

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confidence: 93%

“…An earlier study in this laboratory demonstrated that a pituitary-derived fraction restored the atrophic kidneys of hypophysectomized rats to the weights expected for normal animals of the same body weight (5). Treatment with somatotropin (GH) and corticotropin (ACTH) failed to mimic this effect.…”

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confidence: 98%

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Partial purification and characterization of a renotropic fraction from ovine pituitaries.

Nomura¹,

Puett²,

Nicholson³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

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It has been previously established that hypophysectomy leads to renal atrophy in rats and that a crude pituitaryderived fraction is effective in restoring kidney weight to the level expected for intact animals of the same body weight. This paper reports that considerable purification ofthe crude renotropic fraction from ovine pituitaries has been achieved and that the purified fraction is capable of restoring kidney weights of hypophysectomized castrated rats to normal values. For example, after five daily subcutaneous injections (135 jig/day) there were significant increases in dry kidney weight and total renal protein and DNA. The pituitary-derived fraction was devoid of somatotropin, contained only trace amounts of corticotropin, y-lipotropin, vasopressin, and prolactin, and had only low levels of thyrotropin and follitropin. Daily injections of prolactin, thyrotropin, and follitropin in doses of 20 jig each failed to stimulate renal growth in hypophysectomized rats. Thus, it seems highly unlikely that these factors are responsible for the observed renal hyperplasia after treatment with the pituitary fraction. The purified renotropic fraction had an isoelectric pH between 8 and 9. On polyacrylamide gel electrophoresis in the presence of detergent and a reducing agent, the renotropic fraction exhibited two major bands and one minor band with mobilities that corresponded to those of a standard lutropin preparation. The renotropic fraction exhibited considerable crossreactivity with an antiserum directed against the lutropin a subunit, suggesting the presence of the common glycoprotein hormone subunit. Moreover, the purified fraction stimulated steroid production by Leydig tumor cells in vitra It is noteworthy, however, that standard ovine lutropin at 135 jig/day failed to exhibit renotropic activity in hypophysectomized castrated rats, although effects were noted at twice that dose. It appears that the renotropic activity represents a pituitary substance that can be separated from lutropin only with difficulty.The pituitary is believed to be essential for maintaining normal kidney size because hypophysectomy leads to renal atrophy (1, 2) and prevents the compensatory renal hypertrophy that occurs after unilateral nephrectomy (1,3,4). An earlier study in this laboratory demonstrated that a pituitary-derived fraction restored the atrophic kidneys of hypophysectomized rats to the weights expected for normal animals of the same body weight (5). Treatment with somatotropin (GH) and corticotropin (ACTH) failed to mimic this effect. This renotropic activity was also observed in hypophysectomized castrated rats, demonstrating that the activity was not mediated solely by androgens which are known to stimulate renal growth in rats (6). In addition, human choriogonadotropin (hCG) was ineffective in restoring the renal weight of hypophysectomized castrated rats (5).In an effort toward final purification and characterization of the pituitary-derived renotropin, the crude renotropic fraction from ovine pituitaries h...

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Section: Discussionmentioning

confidence: 53%

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confidence: 93%

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Partial purification and characterization of a renotropic fraction from ovine pituitaries.

Nomura¹,

Puett²,

Nicholson³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

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“…Lactation after the first pregnancy, suggesting prolactin deficiency; however, lactation after subsequent pregnancies is normal (27). Allometry was used to assess change Hormones secreted by the anterior pituitary gland influence in KW because of its advantages in comparing animals of different both normal renal growth (1,13,14,19,38) and compensatory sizes. Estimations of nucleic acids and protein were used to assess renal growth (CRG) (45).…”

Section: Discussionmentioning

confidence: 99%

Compensatory Renal Growth in the Mouse. II. The Effect of Growth Hormone Deficiency

et al. 1981

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Summarysuppressed (21,32,49). Three days after nephrectomy in hypophysectomized rats, tritiated thymidine shows that mitoses are still Allometry was used to study the effect of growth hormone (GH) 60% as frequent as normal and GH only partially restores this deficiency on compensatory renal growth (CRG) in a dwarf mouse deficiency (32), strain (Little). Nucleic acid and protein estimations were used to study of the role of GH is complicated by the postulated assess changes in cellular hyperplasia and hypertrophy. Nephrec-existence of a GH-related "renotrophic factorn (18), for which tomy was ~erformed at 5,15, or 35 days of age with removal of the there is accumulating evidence in vitro (39,43) Of because of its similarity to somatomedin (41) (a proposed "second age was closely related to that of the normal heteroz~gote (lit/ messengern for GH (24), but nonsuppresslble, insulin-like activity +). A regression line for the renoprival kidneys in lit/lit animals actually inhibited CRG in hypophysectomized rats, was parallel to that of the rightStudying the role of GH is further complicated by problems interval between the regression lines was equivalent to a constant that hypophysectomy creates in animal models, One of these is difference of approximately "% between reno~riva' and the ensuing severity of weight loss. Difficulties due to a relatively right kidneys and was similar to that found in the normal hetero-greater loss of kidney weight (KW) (42) in hypophysectomized zygote (43%). Increases in DNA, RNA, and protein in animals, arise when comparing normal animals with those that during CRG indicate that division and have lost weight after hypophysectomy, Such problems are overwere occurring in similar proportions. In the GH-deficient mouse, come by using the allometric relationship between KW and BW the amount Of DNA in renoprival kidneys was 0'451 mg (25). Another problem is the multiple hormone deficiency. Pituicompared with 0.439 mg in (NS). This suggests that tary ablation may obscure the effect that the hormones exert in replication was suppressed. The protein:DNA ratio increased from above and beyond their individual action, To avoid 20.91 to 24.27 (P < 0.001) and the RNA:DNA ratio increased from complications due to hypophysectomy, we chose, instead, to use 0.732 to 0.912 ( P < 0.001), suggesting that cell size was markedly a GH-deficient dwarf mouse strain, increased. These suggest that reduced amounts Of GH The Little mouse (lit), an atellotic dwarf strain (16), was used in may produce a dissociation between h~p'r~lasia and h~~e r t r o~h~, this study, ~h~ animal's autosomal recessive defect appears to be with CRG occurring predominantly by cellular hypertrophy. a selective deficiency of pituitary GH. resembling type 1 GH deficiency in humans (7, 16). The mice do not have neonatal or Speculation pubertal growth spurts, but the females are fertile. They grow with Growth hormone deficiency does not prevent compensatory repetitive pregnancies and can achieve normal weights after mulrenal growth, which occ...

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“…Hypophysectomy has been reported to induce renal atrophy [1,2] and to suppress compensatory renal growth seen in normal intact animals after unilateral nephrec tomy [3], Nicholson et al used a crude ovine pituitary fraction to reverse renal atrophy in castrated hypophys ectomized rats [4], This pituitary fraction was extensively purified in chromatographic steps and the most highly purified frac tion found to resemble lutropin [5], An ovine lutropin preparation purified by the Papkoff and Gan method [6] was found to increase kidney weight in castrated hypo physectomized rats [5], Although human chorionic gon adotropin (hCG) has generally the same biological activ ity as lutropin, no renotropic activity was demonstrated [4], suggesting that the renotropic effect of lutropin might have been due to something other than intrinsic lutropin activity.…”

Section: Introductionmentioning

confidence: 99%

Renotropic Stimulation of DNA Synthesis of Proximal Tubules and Endothelial Cells in the Outer Medulla

Nomura¹,

Mizuhira

Shiihashi

et al. 1985

Nephron

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We explored the effects of ovine pituitary-derived renotropin on renal DNA synthesis in castrated hypophysectomized mice. Administration of the preparation at a dose of 47 μg for 5 days was followed by significant increases in renal DNA (134% of controls), and in kidney dry weight, protein and RNA. A time course study showed that [³H]-thymidine incorporation into renal DNA peaked at 8–10 h after one injection (60 μg) 1.9 times higher than in controls. Autoradiographic studies indicated that labeling indices increased significantly in proximal tubules (17 times) and endothelial cells (4 times) in the outer renal medulla of treated mice compared to controls. Nuclear areas in these cells also increased significantly. Our studies demonstrated a time course of new DNA synthesis stimulated by a renotropin and identified renotropin target cells.

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Evidence for Renotropic Activity in Ovine Pituitaries*

Cited by 18 publications

References 13 publications

Partial purification and characterization of a renotropic fraction from ovine pituitaries.

Partial purification and characterization of a renotropic fraction from ovine pituitaries.

Compensatory Renal Growth in the Mouse. II. The Effect of Growth Hormone Deficiency

Renotropic Stimulation of DNA Synthesis of Proximal Tubules and Endothelial Cells in the Outer Medulla

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