THE EFFECTS OF ORCHIDECTOMY AND TESTOSTERONE PROPIONATE INJECTION ON PEPTIDASE ACTIVITY IN THE MALE RAT HYPOTHALAMUS

1973 ◽  
Vol 72 (1) ◽  
pp. 1-8 ◽  
Author(s):  
E. C. Griffiths ◽  
K. C. Hooper

ABSTRACT It has previously been shown that the activity of certain peptidases in the female rat hypothalamus is related to the release of luteinizing hormone releasing factor from the tissue (Griffiths & Hooper 1972a). The activity of these enzymes was investigated after orchidectomy and testosterone propionate injection to determine if a similar relationship exists in male rats. The depression in supernatant activity following orchidectomy and the elevation after testosterone treatment are interpreted as confirming this, and it is proposed that alterations in peptidase activity may be used as an index of gonadotrophin release in male as well as in female rats.

1973 ◽  
Vol 74 (1) ◽  
pp. 41-48 ◽  
Author(s):  
E. C. Griffiths ◽  
K. C. Hooper

ABSTRACT The activity of peptidases in the rat hypothalamus which are capable of inactivating oxytocin has previously been found to vary with stimuli known to influence gonadotrophin release and may be related to both luteinizing hormone (LH) and luteinizing hormone releasing factor (LH-RF) release (Griffith & Hooper 1972a,b). In the present study, enzyme activity was determined in normal female rats during the morning and afternoon of each stage of the oestrous cycle, in normal rats, and in female rats injected neonatally with testosterone. The activity of the supernatant fraction was found to be not significantly different during the morning of each stage, but was greatly decreased on the afternoon of pro-oestrus; particulate activity did not vary during the oestrous cycle. Supernatant and particulate activities were found to be the same in normal male rats and testosterone-treated females, as previously shown. Both fractions' activities were significantly less than those found in the oestrous cycle, other than on the afternoon of pro-oestrus. These results indicate changes in hypothalamic peptidase activity during the oestrous cycle which may be inversely related to LH and LH-RF release; they also confirm the masculinizing effect of neonatal testosterone on the hypothalamus.


1973 ◽  
Vol 72 (1) ◽  
pp. 9-17 ◽  
Author(s):  
E. C. Griffiths ◽  
K. C. Hooper

ABSTRACT The previous paper (Griffiths & Hooper 1973) described the activity of certain hypothalamic peptidases following orchidectomy and testosterone propionate injection, and suggested that changes in enzyme levels may be used as an index of gonadotrophin release in male rats, in a similar way to that previously described for female rats (Griffiths & Hooper 1972a). Using this approach, the effect of neonatally administered oestrogen on the hypothalamus was investigated. The marked increase in supernatant activity in male rats and the equally marked decrease in supernatant activity in female rats, both injected during the critical period of hypothalamic sexual differentiation, are interpreted as indicating decreased LH secretion in males and increased LH secretion in females respectively. It can be concluded that the changes in reproductive function produced by neonatally administered oestrogen are caused by alterations in LH-RF metabolism and that the peptidases in the rat hypothalamus are responsible for this metabolism.


1998 ◽  
Vol 335 (3) ◽  
pp. 619-630 ◽  
Author(s):  
Philip J. SHERRATT ◽  
Margaret M. MANSON ◽  
Anne M. THOMSON ◽  
Erna A. M. HISSINK ◽  
Gordon E. NEAL ◽  
...  

A characteristic feature of the class Theta glutathione S-transferase (GST) T1-1 is its ability to activate dichloromethane and dibromoethane by catalysing the formation of mutagenic conjugates. The level of the GSTT1 subunit within tissues is an important determinant of susceptibility to the carcinogenic effects of these dihaloalkanes. In the present study it is demonstrated that hepatic GST activity towards these compounds can be elevated significantly in female and male Fischer-344 rats by feeding these animals on diets supplemented with cancer chemopreventive agents. Immunoblotting experiments showed that increased activity towards the dihaloalkanes is associated with elevated levels of the GSTT1 subunit in rat liver. Sex-specific effects were observed in the induction of GSTT1 protein. Amongst the chemopreventive agents tested, indole-3-carbinol proved to be the most potent inducer of hepatic GSTT1 in male rats (6.2-fold), whereas coumarin was the most potent inducer of this subunit in the livers of female rats (3.5-fold). Phenobarbital showed significant induction of GSTT1 only in male rat liver and had little effect in female rat liver. Western blotting showed that class Alpha, Mu and Pi GST subunits are not co-ordinately induced with GSTT1, indicating that the expression of GSTT1 is determined, at least in part, by mechanisms distinct from those that regulate levels of other transferases. The increase in amount of hepatic GSTT1 protein was also reflected by an increase in the steady-state level of mRNA in response to treatment with chemopreventive agents and model inducers. Immunohistochemical detection of GSTT1 in rat liver supported the Western blotting data, but showed, in addition to cytoplasmic staining, significant nuclear localization of the enzyme in hepatocytes from some treated animals, including those fed on an oltipraz-containing diet. Significantly, the hepatic level of cytochrome P-450 2E1, an enzyme which offers a detoxification pathway for dihaloalkanes, was unchanged by the various inducing agents studied. It is concluded that the induction of GSTT1 by dietary components and its localization within cells are important factors that should be considered when assessing the risk dihaloalkanes pose to human health.


1984 ◽  
Vol 103 (3) ◽  
pp. 317-325
Author(s):  
A. K. Brar ◽  
G. Fink

ABSTRACT The effects of catechol oestradiol and catechol oestrone on the release of LH and prolactin were investigated in immature male and female Wistar rats. In male rats both catechol oestradiol and catechol oestrone significantly increased the plasma concentration of LH, and catechol oestradiol but not catechol oestrone significantly increased the plasma concentration of prolactin and decreased the pituitary concentration of LH. The parent oestrogens, oestradiol-17β and oestrone, had no effect on plasma LH concentrations, but both increased significantly the plasma concentration of prolactin, and oestrone but not oestradiol-17β increased the pituitary concentration of LH. In immature female rats, catechol oestradiol inhibited the surge of LH and the increase in uterine weight induced by injecting pregnant mare serum gonadotrophin (PMSG). The injection of oestrone induced an increase in the plasma concentration of LH which was about nine times greater than that produced by oestradiol-17β. There were no significant differences in the effects of these steroids on plasma prolactin concentration. These results (i) confirm that in the immature male rat catechol oestrogens can stimulate LH release and show that catechol oestradiol can increase prolactin release, (ii) show that catechol oestradiol can inhibit the stimulatory effects of PMSG on LH release and uterine weight in the immature female rat, and (iii) demonstrate that oestrone can stimulate LH release in the immature female rat. J. Endocr. (1984) 103, 317-325


1972 ◽  
Vol 69 (2) ◽  
pp. 249-256 ◽  
Author(s):  
E. C. Griffiths ◽  
K. C. Hooper

ABSTRACT Previous work in the rabbit has shown that the activity of certain peptidases in the hypothalamus which inactivate oxytocin, changes with stimuli known to release gonadotrophins, and may be used as an index of gonadotrophin hormone release (Hooper 1966a,b, 1968; Frith & Hooper 1971a,b). Using this approach, a study was made of the activities of similar peptidases in the rat hypothalamus following ovariectomy, a condition known to cause gonadotrophin release. Enzyme activity in the supernatant fraction was found to decrease progressively with time after ovariectomy, until 42 days after operation, thereafter maintaining a level not significantly different from that at 42 days; there was no detectable difference in particulate enzyme activity after ovariectomy. An inverse relationship between supernatant enzyme activity and luteinizing hormone levels is suggested. It is concluded that a similar relationship to that in the rabbit exists between enzyme activity in the rat hypothalamus and the release of luteinizing hormone-releasing factor from the tissue.


1974 ◽  
Vol 77 (3) ◽  
pp. 435-442 ◽  
Author(s):  
E. C. Griffiths ◽  
K. C. Hooper ◽  
S. L. Jeffcoate ◽  
D. T. Holland

ABSTRACT The presence of peptidases in the rat hypothalamus inactivating luteinizing hormone-releasing hormone (LH-RH) has previously been demonstrated using an indirect assay method. With the development of a sensitive and specific radioimmunoassay for the releasing hormone, this technique was employed in the study of the peptidases inactivating LH-RH. It was found that supernatant fractions from both male and female rat hypothalami rapidly inactivated LH-RH, and that the peptidase activity of the supernatant fraction was higher in male than in female animals though the particulate fraction's activity was about the same in both sexes. Peptidase activity was also considerably greater in the supernatant than in the particulate fraction. These results confirm that the hypothalamus contains peptidases capable of inactivating LH-RH and give a direct indication that the enzymes may be involved in the central nervous system's control of reproductive function.


1956 ◽  
Vol 34 (1) ◽  
pp. 903-911
Author(s):  
J. D. McColl ◽  
J. M. Parker ◽  
J. K.W. Ferguson

The diuretic response of the male and the female rat to aminophylline has been studied when these animals were pretreated with various concentrations of sodium chloride solution. A linear log dose – response curve was obtained over the dose range employed with male rats pretreated with 0.45% and 2% saline. Male rats exhibited a diuresis with 4% saline which was not increased by aminophylline. Female rats showed diuresis but the responses were more variable for almost all combinations of electrolyte load and xanthine dose. When they were pretreated with 0.45% and 2% saline, aminophylline caused some additional production of urine but this was much less regular than that observed with males. The variation in response to aminophylline after 4% saline was very marked but the trend suggested that the xanthine had a diuretic effect at the high dose. The diuretic responses to a xanthine, a mercurial, and a carbonic anhydrase inhibitor type of diuretic were compared in the male rat. Peak responses were smallest after the mercurial diuretic and greatest with the carbonic anhydrase inhibitor.


1975 ◽  
Vol 80 (2) ◽  
pp. 319-328
Author(s):  
R. S. Leeuwin ◽  
B. J. Visser ◽  
C. v. d. Meer

ABSTRACT Using the extraction procedure of Schmidt & Thannhauser (1945) and the indole reaction for DNA according to Ceriotti (1952), the DNA content of female rat liver was about one and a half times that of male liver. Castration of male rats, with or without administration of testosterone propionate, had no effect on the liver DNA content. Spaying of female rats (5–6 weeks of age) caused a decrease of the liver DNA content. Substitution with oestradiol benzoate restored the amount of DNA. No significant sex difference was observed in the DNA content of either rat brain, kidney, spleen and thymus, or mouse liver. Dische's diphenylamine reaction showed no significant sex difference in the rat liver DNA content. It was concluded that rat liver may contain a substance which is controlled by oestrogens and which interferes with the indole reaction. The interfering factor is present in the protein fraction of the liver extract. The possible nature of this interfering substance is discussed.


2017 ◽  
Vol 233 (2) ◽  
pp. 187-196 ◽  
Author(s):  
Marion Walser ◽  
Linus Schiöler ◽  
Jan Oscarsson ◽  
Maria A I Åberg ◽  
Ruth Wickelgren ◽  
...  

The endogenous secretion of growth hormone (GH) is sexually dimorphic in rats with females having a more even and males a more pulsatile secretion and low trough levels. The mode of GH administration, mimicking the sexually dimorphic secretion, has different systemic effects. In the brains of male rats, we have previously found that the mode of GH administration differently affects neuron–haemoglobin beta (Hbb) expression whereas effects on other transcripts were moderate. The different modes of GH administration could have different effects on brain transcripts in female rats. Hypophysectomised female rats were given GH either as injections twice daily or as continuous infusion and GH-responsive transcripts were assessed by quantitative reverse transcription polymerase chain reaction in the hippocampus and parietal cortex (cortex). The different modes of GH-administration markedly increased Hbb and 5′-aminolevulinate synthase 2 (Alas2) in both brain regions. As other effects were relatively moderate, a mixed model analysis (MMA) was used to investigate general effects of the treatments. In the hippocampus, MMA showed that GH-infusion suppressed glia- and neuron-related transcript expression levels, whereas GH-injections increased expression levels. In the cortex, GH-infusion instead increased neuron-related transcripts, whereas GH-injections had no significant effect. Interestingly, this contrasts to previous results obtained from male rat cortex where GH-infusion generally decreased expression levels. In conclusion, the results indicate that there is a small but significant difference in response to mode of GH administration in the hippocampus as compared to the cortex. For both modes of GH administration, there was a robust effect on Hbb and Alas2.


1956 ◽  
Vol 34 (5) ◽  
pp. 903-911 ◽  
Author(s):  
J. D. McColl ◽  
J. M. Parker ◽  
J. K.W. Ferguson

The diuretic response of the male and the female rat to aminophylline has been studied when these animals were pretreated with various concentrations of sodium chloride solution. A linear log dose – response curve was obtained over the dose range employed with male rats pretreated with 0.45% and 2% saline. Male rats exhibited a diuresis with 4% saline which was not increased by aminophylline. Female rats showed diuresis but the responses were more variable for almost all combinations of electrolyte load and xanthine dose. When they were pretreated with 0.45% and 2% saline, aminophylline caused some additional production of urine but this was much less regular than that observed with males. The variation in response to aminophylline after 4% saline was very marked but the trend suggested that the xanthine had a diuretic effect at the high dose. The diuretic responses to a xanthine, a mercurial, and a carbonic anhydrase inhibitor type of diuretic were compared in the male rat. Peak responses were smallest after the mercurial diuretic and greatest with the carbonic anhydrase inhibitor.


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