PEPTIDASE ACTIVITY IN DIFFERENT AREAS OF THE RAT HYPOTHALAMUS

1974 ◽  
Vol 77 (1) ◽  
pp. 10-18 ◽  
Author(s):  
E. C. Griffiths ◽  
K. C. Hooper

ABSTRACT To provide further information on the function of peptidases present in the rat hypothalamus which are capable of inactivating oxytocin, these enzymes' activity was investigated in anterior, middle and posterior hypothalamic areas of normal male and female rats, gonadectomized rats and rats gonadectomized and injected with gonadal steroids (oestradiol in female animals, testosterone in males). Peptidase activity in the supernatant fraction was distributed unevenly through the hypothalamus with the majority of activity in the anterior and middle areas from both sexes; particulate peptidase activity occurred principally in the middle and posterior areas. Gonadectomy selectively decreased supernatant activity in the anterior and middle areas, whereas steroid treatment reversed this effect, but neither caused any change in particulate activity from female rats and only small changes in male animals. These results are interpreted as indicating a selective distribution of supernatant peptidase activity in those hypothalamic areas responsible for luteinizing hormone – releasing factor (LRF) synthesis and release, and confirming previous findings that this fraction may be involved in LRF metabolism. They may also suggest the sites of gonadal steroid feedback at the hypothalamic level.

1975 ◽  
Vol 79 (1) ◽  
pp. 209-216 ◽  
Author(s):  
E. C. Griffiths ◽  
K. C. Hooper ◽  
S. L. Jeffcoate ◽  
N. White

ABSTRACT Peptidases capable of inactivating thyrotrophin-releasing hormone (TRH) have been demonstrated in the hypothalamus. With the development of a specific radioimmunoassay for TRH, this method was used to further study the enzymes acting on the releasing hormone. Whole hypothalamic homogenates from male and female rats inactivated TRH, with greater peptidase activity being found in the female animals. Separation of the homogenates into particulate (microsomal and mitochondrial) and supernatant (soluble/cytoplasmic) fractions showed approximately the same amounts of enzyme activity in both fractions, while dialysis of the fractions slightly reduced the TRH peptidase activity present, suggesting that a diffusible co-factor might be partially involved in the releasing hormone's degradation. These results confirm the presence of TRH-inactivating peptidases in the rat hypothalamus and suggest that the enzymes may be involved in some way in the mechanisms by which the brain controls thyrotrophin release by the anterior pituitary.


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.


Endocrinology ◽  
2014 ◽  
Vol 155 (1) ◽  
pp. 204-214 ◽  
Author(s):  
Danielle M. Cusmano ◽  
Maria M. Hadjimarkou ◽  
Jessica A. Mong

The paucity of clinical and preclinical studies investigating sex differences in sleep has resulted in mixed findings as to the exact nature of these differences. Although gonadal steroids are known to modulate sleep in females, less is known about males. Moreover, little evidence exists concerning the origin of these sex differences in sleep behavior. Thus, the goal of this study was to directly compare the sensitivity of sleep behavior in male and female Sprague Dawley rats to changes in the gonadal steroid milieu and to test whether the sex differences in sleep are the result of brain sexual differentiation or differences in circulating gonadal steroids. Here we report the magnitude of change in sleep behavior induced by either estradiol (E2) or testosterone (T) was greater in females compared with males, suggesting that sleep behavior in females is more sensitive to the suppressive effects of gonadal steroids. Furthermore, we demonstrated that the organizational effects of early gonadal steroid exposure result in male-like responsivity to gonadal steroids and directly alter the activity of the ventrolateral preoptic area (VLPO), an established sleep-promoting nucleus, in adult masculinized females. Moreover, the nonaromatizable androgen dihydrotestosterone did not suppress sleep in either males or females, suggesting that the T-mediated effect in females was due to the aromatization of T into E2. Together our data suggest that, like sex behavior, sex differences in sleep follow the classical organizational/activational effects of gonadal steroids.


1972 ◽  
Vol 53 (1) ◽  
pp. 47-57 ◽  
Author(s):  
C. M. TAPPER ◽  
F. NAFTOLIN ◽  
K. BROWN-GRANT

SUMMARY The changes in plasma luteinizing hormone (LH) concentration during the first few days after ovariectomy in the rat differ according to the stage of the cycle at which the operation is performed. When carried out at oestrus there was no increase in LH concentration in the first 4 days. After operation at metoestrus the concentration was increased at 3 days but not earlier. Ovariectomy at dioestrus resulted in an immediate increase after 8 h, a subsequent fall, though not to basal levels, and a fairly steady rise thereafter. Ovariectomy at pro-oestrus produced a very large initial rise in plasma LH which probably represents an accelerated release of the ovulatory surge of LH rather than a specific response to ovariectomy. At 24 h after ovariectomy at pro-oestrus levels were below normal and did not increase again for a further 3 days. In contrast, male rats showed a rapid and sustained rise in plasma LH concentration after castration. It is suggested that the different patterns seen in the female may be related to the time that elapsed since the hypothalamo—pituitary system was exposed to high levels of circulating oestradiol. The changes in plasma LH concentration observed after ovariectomy in neonatally androgen-treated rats, rats in persistent oestrus due to exposure to constant light, and rats in early pregnancy are consistent with this hypothesis. Differing responses to the administration of sodium pentobarbitone between male and female rats even 21 days after gonadectomy suggest that there may also be differences in this negative feedback system between the two sexes that are independent of the nature of the gonadal steroid secreted.


1992 ◽  
Vol 132 (1) ◽  
pp. 39-45 ◽  
Author(s):  
A. C. Dalkin ◽  
S. J. Paul ◽  
D. J. Haisenleder ◽  
G. A. Ortolano ◽  
M. Yasin ◽  
...  

ABSTRACT Gonadal steroids can act both indirectly via gonadotrophin-releasing hormone (GnRH) and directly on the pituitary to regulate gonadotrophin subunit gene expression. Recent studies to assess a possible direct action at the pituitary have shown that testosterone, when given to males in the absence of endogenous GnRH action, selectively increases FSH-β mRNA concentrations. Conversely, in females, oestradiol appears to regulate gonadotrophin subunit mRNAs primarily via GnRH. The present study was designed to determine whether these differing results reflect specific actions of the gonadal steroids themselves or different responses of the pituitary gonadotroph cells in males and females. Rats which had been castrated 7 days earlier were given silicone elastomer implants (s.c.) containing oestradiol (plasma oestradiol 68 ± 4 ng/l) in males or testosterone (plasma testosterone 3·5 ± 0·3 μg/l) in females in the absence or presence of a GnRH antagonist. Seven days later pituitaries were removed and steady-state mRNA concentrations measured by dotblot hybridization. In males, oestradiol reduced LH-β and FSH-β but not α mRNA. The antagonist reduced levels of all three subunit mRNAs in males and the addition of oestradiol had no further effect, suggesting that oestradiol regulates gonadotrophin subunit gene expression in males by suppressing GnRH secretion. In females, testosterone reduced all three subunit mRNAs though FSH-β remained threefold higher than in intact animals. The GnRH antagonist was as effective as testosterone alone and reduced α and LH-β to levels found in intact animals. FSH-β mRNA was partially reduced by antagonist alone in ovariectomized females but the addition of testosterone increased FSH-β twofold versus antagonist alone (as has been observed in males). These findings, together with earlier data, suggest that testosterone increased FSH-β twofold versus antagonist alone (as has been observed in males). These findings, together with earlier data, suggest that testosterone reduces gonadotrophin subunit mRNAs by inhibiting GnRH secretion and also acts directly on the gonadotroph to increase steady-state FSH-β mRNA concentrations in both males and females. Journal of Endocrinology (1992) 132, 39–45


1985 ◽  
Vol 41 (3) ◽  
pp. 237-245 ◽  
Author(s):  
Charles W. Scouten ◽  
William E. Heydorn ◽  
G. Joseph Creed ◽  
Charles W. Malsbury ◽  
David M. Jacobowitz

1976 ◽  
Vol 68 (2) ◽  
pp. 265-272 ◽  
Author(s):  
ÅKE STENBERG

SUMMARY The metabolism of [4-14C]4-androstene-3,17-dione was studied in the 105000 g microsomal and supernatant fractions of liver from developing rats of both sexes. The following enzyme activities were measured: 5β-reductase (supernatant fraction) and 5α-reductase, 17α- and 17β-hydroxysteroid reductases, 6β-, 7α- and 16α-hydroxylases (microsomal fraction). The activities of the 3α- and 3β-hydroxysteroid reductases were estimated by calculating the ratios of 3α-:5α- and 3β-: 5α-reduced metabolites formed, respectively. Most enzyme activities present at birth (i.e. 5β-reductase, 5α-reductase, 17β-hydroxysteroid reductase, 6β- and 7α-hydroxylase) increased until 20 days of age in both male and female rats. Between 20 and 30 days of age a number of masculine metabolic characteristics appeared in both sexes, i.e. the 16α-hydroxylase and the 17α-hydroxysteroid reductase were induced, the 5β-reductase activity rapidly increased and the 5α-reductase activity slightly decreased. During a third period beginning 30 days after birth the adult male enzyme activity pattern was completed by the induction of 3β-hydroxysteroid reductase and a further increase in the activity of 16α-hydroxylase. After 30 days of age a feminine type of liver metabolism also rapidly developed in female rats; the 16α-hydroxylase and the 17α-hydroxysteroid reductase activities disappeared, the 6β-hydroxylase and the 5β-reductase activities decreased and the 5α-reductase activity increased six times. The developmental patterns of enzyme activities in the rat liver are consistent with a first developmental phase (0–30 days of age) independent of hypophysial control and probably determined primarily by the genome of the liver cell and a second phase (from 30 days onwards) with increasing sexual differentiation under hypophysial control. This control is mediated by some kind of feminizing factor in female rats and possibly by some kind of androgen-elicited secretion of masculinizing factor(s) in male rats. The metabolism of [4-14C]4-androstene-3,17-dione was also studied during different times of the day and during different phases of the oestrous cycle. The 16α-hydroxylase activity showed a diurnal variation with higher values at noon than at midnight. The 5β-reductase activity reached a maximal activity during metoestrus.


2008 ◽  
Vol 89 (3) ◽  
pp. 314-323 ◽  
Author(s):  
Sarah L. Parylak ◽  
Joseph M. Caster ◽  
Q. David Walker ◽  
Cynthia M. Kuhn

1977 ◽  
Vol 74 (3) ◽  
pp. 375-382 ◽  
Author(s):  
J. T. M. VREEBURG ◽  
PAULA D. M. VAN DER VAART ◽  
P. VAN DER SCHOOT

SUMMARY An inhibitor of aromatization, androsta-1,4,6-triene-3,17-dione (ATD), was administered to newborn male and female rats and various parameters of gonadal and sexual function were examined in adulthood. Males injected with 1 mg ATD on the day of birth (day 1) and on days 3, 5, 10 and 15 postnatally, subsequently (day 55) showed normal male and female copulatory behaviour, but were not able to maintain cyclicity in ovarian transplants. When the ATD was administered by Silastic implants, however, cyclicity in ovarian transplants did occur. Neither form of treatment brought about significant changes in neonatal plasma or testicular testosterone concentrations. Female rats implanted on day 3 of life with Silastic capsules containing ATD and then given an injection of 0·25 mg testosterone propionate on day 5 subsequently showed normal ovarian function, whereas the controls receiving only testosterone propionate showed persistent vaginal cornification, anovulation and polyfollicular ovaries. The results support the view that the central conversion of testicular androgens to oestrogens during the neonatal period is necessary to abolish cyclic gonadotrophin release and to suppress female copulatory behaviour.


Sign in / Sign up

Export Citation Format

Share Document