Growth hormone responses to multiple injections of a fragment of human growth hormone-releasing factor in conscious male and female rats

1985 ◽  
Vol 106 (3) ◽  
pp. 281-289 ◽  
Author(s):  
R. G. Clark ◽  
I. C. A. F. Robinson

ABSTRACT The GH responses to single i.v. injections of GH-releasing factor (GRF) in conscious male rats are highly variable. Although normal male rats show a pulsatile secretory pattern of GH with pulses occurring at intervals of 3–3·5 h, the peaks occur at different times in individual animals. We have compared the GH responses of young conscious male and female rats to multiple i.v. injections of 1 μg human (h) GRF1-29NH2. The peak GH responses occurred 3–5 min after hGRF1-29NH2 injection and were lower in female than in male rats. Both males and females responded uniformly to hGRF1-29NH2 injections given 180 min apart and the GH responses became entrained with no endogenous GH pulsing. Female rats produced consistent GH peaks in response to hGRF1-29NH2 injections at 90-min intervals, whereas male rats responded only to alternate injections, so that GH peaks occurred only every 180 min despite giving GRF every 90 min. When the frequency of hGRF1-29NH2 administration was increased to once every 40 min female rats again responded consistently to each injection. Male rats responded intermittently, being able to respond to two injections 40 min apart, after which they became refractory to hGRF1-29NH2. This cycle of varying sensitivity to GRF in male rats probably underlies their 3-hourly endogenous GH secretory rhythm. Female rats can respond uniformly to repeated GRF injections, consistent with their more continuous pattern of endogenous GH secretion. Introducing a pulse of 10 μg rat GH into a series of hGRF1-29NH2 injections did not induce refractoriness to hGRF1-29NH2, suggesting that GH does not itself desensitize the pituitary to GRF. Whether the different patterns of GH secretion in males and females result from different patterns of GRF and/or somatostatin secretion remains to be determined. J. Endocr. (1985) 106, 281–289

1990 ◽  
Vol 126 (1) ◽  
pp. 27-35 ◽  
Author(s):  
L. M. S. Carlsson ◽  
R. G. Clark ◽  
I. C. A. F. Robinson

ABSTRACT Growth hormone inhibits its own secretion in animals and man but the mechanism for this inhibition is unclear: both stimulation of somatostatin release and inhibition of GH-releasing factor (GRF) release have been implicated. We have now studied the GRF responsiveness of conscious male and female rats under conditions of GH feedback induced by constant infusion of exogenous human GH (hGH). Intravenous infusions of hGH (60 μg/h) were maintained for 3 to 6 h whilst serial injections of GRF(1–29)NH2 (0·2–1 μg) were given at 45-min intervals. The GH responses were studied by assaying blood samples withdrawn at frequent intervals using an automatic blood sampling system. We have confirmed that male and female rats differ in their ability to respond to a series of GRF injections; female rats produced consistent GH responses for up to 13 consecutive GRF injections, whereas male rats showed a 3-hourly pattern of intermittent responsiveness. In female rats, multiple injections of GRF continued to elicit uniform GH responses during hGH infusions, whereas hGH infusions in male rats disturbed their intermittent pattern of responsiveness to GRF, and their regular 3-hourly cycle of refractoriness was prolonged. We suggest that this sex difference in GH feedback may be due to GH altering the pattern of endogenous somatostatin release differentially in male and female rats. Such a mechanism of GH autofeedback could be involved in the physiological control of the sexually differentiated pattern of GH secretion in the rat. Journal of Endocrinology (1990) 126, 27–35


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.


1953 ◽  
Vol 31 (1) ◽  
pp. 18-40 ◽  
Author(s):  
Jules Tuba

Liver glucuronidase activity was studied in male and female rats with regard to the effect of a number of experimental factors. Virgin female and breeder female rats had significantly higher levels of the liver enzyme than males. Breeding and lactation stimulated production of liver glucuronidase and activity fell towards male values in females which had passed the breeding age. Castration of males or females had no significant effect on the enzyme. A highly significant elevation of liver glucuronidase resulted from injection of oestradiol dipropionate into castrate male rats, while testosterone dipropionate had no effect. Neither hormone affected activity of the enzyme when injected into normal male or female rats. Levels of liver glucuronidase in diabetic male rats were elevated about 50% above normal, and these statistically significant increases are assumed to be related to some hormonal imbalance


Salud Mental ◽  
2020 ◽  
Vol 43 (1) ◽  
pp. 3-9
Author(s):  
Adriana Álvarez Silva ◽  
Alonso Fernández-Guasti

Introduction. Depression is a global health problem with nearly 350 million people affected, mainly women. However, nowadays a rising amount of men are being diagnosed. This makes necessary the screening of new treatment options that are effective in women as well as in men. Objective. To analyze if the administration of mirtazapine and venlafaxine to male and female rats shows a sex-related antidepressant-like effect, and the possible associated neurochemical mechanisms. Method. Mirtazapine (40 mg/kg) or venlafaxine (60 mg/kg) were administered subchronically to young adult male and female (ovariectomized and steroid-primed) rats, and their antidepressant-like effects were evaluated using the forced swim test (FST). The active behaviors, swimming and climbing, were also analyzed. Results. a) mirtazapine and venlafaxine reduced immobility in the FST in males and females; b) both antidepressants increased climbing and swimming in male rats; c) in female rats, mirtazapine and venlafaxine only increased swimming. Discussion and conclusion. In males, the effects of mirtazapine and venlafaxine seem to be produced by the activation of the serotonergic and noradrenergic systems. Conversely, estradiol might be modulating the mechanisms of action of both antidepressants in females producing only an increased swimming and suggesting the participation of the serotonergic system.


Endocrinology ◽  
1998 ◽  
Vol 139 (8) ◽  
pp. 3590-3596 ◽  
Author(s):  
Danielle F. Carmignac ◽  
Pamela A. Bennett ◽  
Iain C. A. F. Robinson

Abstract In addition to stimulating GH release, GH secretagogues such as GH-releasing peptide-6 (GHRP-6) stimulate small amounts of ACTH and PRL release. Although the effects on ACTH have recently been studied, there is little information about the effects of GHRP-6 on PRL. We have now studied GHRP-6-induced GH and PRL release and their regulation by estrogen (E2) in anesthetized male and female rats and in GH-deficient dwarf (dw/dw) rats that maintain high pituitary PRL stores and show elevated hypothalamic GH secretagogue receptor expression. Whereas GHRP-6 (0.1–2.5 μg, iv) did not induce PRL release in normal male or female rats, significant PRL responses were observed in dw/dw females. These responses were abolished by ovariectomy and could be strongly induced in male dw/dw rats by E2 treatment. These effects could be dissociated from GHRP-6-induced GH release in the same animals, but not from PRL release induced by TRH, which was also abolished by ovariectomy and induced in males by E2 treatment. However, the effects of GHRP-6 on PRL were unlikely to be mediated by TRH because in the same animals, TSH levels were unaffected by GHRP-6 whereas they were increased by TRH. The increased PRL response could reflect an increase in GH secretagogue receptor expression that was observed in the arcuate and ventromedial nuclei of E2-treated rats. Our results suggest that the minimal PRL-releasing activity of GHRP-6 in normal rats becomes prominent in GH-deficient female dw/dw rats and is probably exerted directly at the pituitary; these GHRP-6 actions may be modulated by E2 at both hypothalamic and pituitary sites.


1976 ◽  
Vol 69 (2) ◽  
pp. 255-262 ◽  
Author(s):  
M. S. AIYER ◽  
M. C. SOOD ◽  
K. BROWN-GRANT

SUMMARY Rats gonadectomized 1–2 months previously were anaesthetized with sodium pentobarbitone and 50 ng/100 g body weight of a synthetic decapeptide gonadotrophin releasing factor (LH-RF) injected intravenously. Plasma concentrations of LH and FSH were determined by radioimmunoassay in samples taken before and at intervals up to 60 min after the injection of LH-RF. The pituitary response was evaluated by determining the maximal increment in plasma gonadotrophin concentrations and by estimating the area under the plasma gonadotrophin concentration curves. In both males and females the pituitary response was increased in animals given 20 μg oestradiol benzoate 3 days earlier. Progesterone (2·5 mg) had no effect on the response measured 4 h later in oil-treated rats, male or female. In oestrogen-primed rats progesterone administration produced a significantly increased response in females that was not seen if sodium pentobarbitone was given at the time of progesterone injection. In oestrogen-primed males progesterone produced some increase in sensitivity but less than was seen in females. Both in males and in females that had received androgen on day 4 of postnatal life sodium, pentobarbitone had no effect on the responses of oestrogen plus progesterone-treated rats to LH-RF. When two injections of LH-RF were given 60 min apart, the second response was greater than the first in animals, both male and female, that had been primed with oestrogen. The second response was no greater than the first in oil-treated females. The results suggest that oestrogen can increase pituitary sensitivity to LH-RF in both male and female rats and that LH-RF itself can increase pituitary sensitivity to a second injection of LH-RF in both male and female rats if they have received oestrogen. It is suggested that the differences between the pituitary responses of females and males after oestrogen plus progesterone treatment and the major differences in gonadotrophin secretion reported previously (Brown-Grant, 1974) may be accounted for on the basis of there being a relatively slight increase in endogenous LH-RF secretion with a consequent marked rise in pituitary responsiveness in female but not in male rats.


1988 ◽  
Vol 119 (2) ◽  
pp. 201-209 ◽  
Author(s):  
R. G. Clark ◽  
L. M. S. Carlsson ◽  
I. C. A. F. Robinson

ABSTRACT The negative-feedback effects of GH on its own secretion were studied in conscious male and female rats bearing indwelling double-bore venous cannulae. Intravenous infusions of human GH (hGH; 20–60 μg/h) or somatostatin (SS; 10 μg/h) were given while frequent serial microsamples of blood were withdrawn using an automatic blood-sampling system. In both sexes, i.v. infusions of hGH for 6 h inhibited endogenous GH secretory pulses, with a slow onset of the inhibition. There was no rebound GH secretion immediately following the removal of the hGH infusion, but spontaneous GH secretion gradually returned to normal. Infusions of hGH did not inhibit the pituitary GH response to repeated GH-releasing factor (GRF) injections (1 μg) given i.v. every 40 min to female rats. By contrast, infusions of SS, which also blocked spontaneous GH release, dramatically reduced the GH responses to serial GRF injections. When SS Infusions were stopped, the subsequent GRF-induced GH secretory responses were enhanced. These results show that GH can inhibit its own release when given by i.v. infusion to conscious male and female rats. Since GH responses to GRF are maintained during a GH infusion, the feedback effect of GH is unlikely to be exerted directly on the pituitary or by increasing SS release. Our results are consistent with the idea that GH feedback in the conscious rat involves an inhibition of GRF release. J. Endocr. (1988) 119, 201–209


1987 ◽  
Vol 113 (2) ◽  
pp. 249-253 ◽  
Author(s):  
L. Ohlsson ◽  
O. Isaksson ◽  
J.-O. Jansson

ABSTRACT The influence of endogenous gonadal steroids in male and female rats on basal and growth hormone-releasing factor (GRF)-stimulated GH secretion from perifused anterior pituitaries was studied. After 75 min of perifusion with basal medium, freshly dissected pituitaries were exposed to human GRF(1–44) (10 nmol/l) for 15 min. Neonatal (day 1–2) or prepubertal (day 25) gonadectomy of male rats suppressed baseline GH release (ng/min per mg dry weight) as well as GRF-stimulated GH release by 40–70%. This effect was slightly more pronounced in neonatally gonadectomized animals. In prepubertally gonadectomized male rats, the suppression of GH release was completely reversed by testosterone replacement therapy. In female rats, prepubertal gonadectomy did not affect GH secretion from perifused pituitaries. However, treatment of ovariectomized female rats with oestradiol reduced baseline and GRF-induced GH release to levels lower than those observed in sham-operated or vehicle-treated ovariectomized animals. The data suggest that testicular androgen secretion in adult male rats increases the pituitary GH release in response to GRF in vitro, whereas ovarian oestrogen secretion is of less importance for the GRF responsiveness of female rat pituitaries. J. Endocr. (1987) 113,249–253


1975 ◽  
Vol 64 (2) ◽  
pp. 249-255 ◽  
Author(s):  
A. S. GOLDMAN ◽  
A. W. ROOT ◽  
G. DUCKETT ◽  
B. H. SHAPIRO

SUMMARY Pituitary content or concentration of follicle-stimulating hormone (FSH), prolactin and growth hormone in the genetically androgen insensitive male rat pseudohermaphrodite is intermediate between normal male and female rats, while pituitary luteinizing hormone (LH) concentration and serum FSH levels are the same as in the normal male. The concentration of serum LH, prolactin and growth hormone indicates no sexual dimorphism. Although the pseudohermaphrodite is genetically male with a female phenotype, our results suggest some degree of masculinization of the hypothalamicpituitary system.


1973 ◽  
Vol 74 (1) ◽  
pp. 88-104 ◽  
Author(s):  
T. Jolín ◽  
M. J. Tarin ◽  
M. D. Garcia

ABSTRACT Male and female rats of varying ages were placad on a low iodine diet (LID) plus KClO4 or 6-propyl-2-thiouracil (PTU) or on the same diet supplemented with I (control rats). Goitrogenesis was also induced with LID plus PTU in gonadectomized animals of both sexes. The weight of the control and goitrogen treated animals, and the weight and iodine content of their thyroids were determined, as well as the plasma PBI, TSH, insulin and glucose levels. The pituitary GH-like protein content was assessed by disc electrophoresis on polyacrylamide gels. If goitrogenesis was induced in young rats of both sexes starting with rats of the same age, body weight (B.W.) and pituitary growth hormone (GH) content, it was found that both the males and females developed goitres of the same size. On the contrary, when goitrogenesis was induced in adult animals, it was found that male rats, that had larger B.W. and pituitary GH content than age-paired females, developed larger goitres. However, both male and female rats were in a hypothyroid condition of comparable degree as judged by the thyroidal iodine content and the plasma PBI and TSH levels. When all the data on the PTU or KClO4-treated male and female rats of varying age and B.W. were considered together, it was observed that the weights of the thyroids increased proportionally to B.W. However, a difference in the slope of the regression of the thyroid weight over B.W. was found between male and female rats, due to the fact that adult male rats develop larger goitres than female animals. In addition, in the male rats treated with PTU, gonadectomy decreased the B.W., pituitary content of GH-like protein and, concomitantly, the size of the goitre decreased; an opposite effect was induced by ovariectomy on the female animals. However, when goitrogenesis was induced in weight-paired adult rats of both sexes, the male animals still developed larger goitres than the females. Among all the parameters studied here, the only ones which appeared to bear a consistent relationship with the size of the goitres in rats of different sexes, treated with a given goitrogen, were the rate of body growth and the amount of a pituitary GH-like protein found before the onset of the goitrogen treatment. Moreover, though the pituitary content of the GH-like protein decreased as a consequence of goitrogen treatment, it was still somewhat higher in male that in female animals. The present results suggest that GH may somehow be involved in the mechanism by which male and female rats on goitrogens develop goitres of different sizes, despite equally high plasma TSH levels.


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