scholarly journals RF9 Rescues Cortisol-Induced Repression of Testosterone Levels in Adult Male Macaques

2021 ◽  
Vol 12 ◽  
Author(s):  
Rahim Ullah ◽  
Rabia Naz ◽  
Aalia Batool ◽  
Madiha Wazir ◽  
Tanzil Ur Rahman ◽  
...  

Cortisol inhibits hypothalamic-pituitary-gonadal (HPG) axis whereas RF9, a potent agonist of kisspeptin receptor (GPR54) activates HPG-axis during fasting-induced stress and under normal physiological conditions. However, the effect of RF9 on the cortisol-induced repressed HPG-axis is not studied yet. This study investigated whether exogenous cortisol-induced repression of the HPG-axis can be rescued by RF9. Six intact adult male rhesus monkeys (Macaca mulatta) habituated to chair-restraint were administered hydrocortisone sodium succinate at a rate of 20 mg/kg of body weight (BW) per day for 12 days. Single blood sample was taken by venipuncture from each animal on alternate days for hormones analyses. On experimental day 12, hydrocortisone treated monkeys received a single intravenous bolus of RF9 (n = 3) and vehicle (n = 3). The animals were bled for a period of 4 h at 60 min intervals from an indwelling cannula in the saphenous vein. RF9 was administered intravenously at the dose of 0.1 mg/kg BW immediately after taking 0 min sample. Plasma cortisol and testosterone concentrations were measured by using specific enzyme immunoassays. Hydrocortisone treatment increased plasma cortisol levels (P ≤ 0.0001) and decreased plasma testosterone (P ≤ 0.0127) levels. Interestingly, compared to vehicle, RF9 treatment significantly increased plasma testosterone levels at 120 min (P ≤ 0.0037), 180 min (P ≤ 0.0016), and 240 min (P ≤ 0.0001) intervals in the hydrocortisone treated monkeys. From these results, we concluded that RF9 administration relieves the suppressed HPG-axis in term of plasma testosterone levels in the cortisol treated monkeys.

Author(s):  
Aalia Batool ◽  
Madiha Wazir ◽  
Rahim Ullah ◽  
Aalia Batool ◽  
Rabia Naz ◽  
...  

Stress represses hypothalamic-pituitary-gonadal axis (HPG-axis) but RF9, a synthetic peptide, rescues such repression. To assess the role of RF9 in regulating HPG-axis under normal physiological conditions in higher primates, RF9 was administered to intact adult male rhesus monkeys and response of the HPG-axis was examined by measuring plasma testosterone as an end parameter of the axis. Control group (n=4) received normal saline whereas the treated group (n=4) received RF9. On the first day of experiment, four bolus injections of normal saline (1ml/animal) were administered intravenously at 2-hr interval to the control monkeys. Similarly, on the second day of experiment, treated group received four iv bolus injections of RF9 (0.1mg/kg BW) at 2-hr interval. Serial blood samples were collected at 20 min interval during a 6-hr period which started just after first saline/RF9 injection. Plasma testosterone levels were measured by using a specific EIA. Overall means of plasma testosterone levels and plasma testosterone area under curve (AUC) and overall mean testosterone and mean testosterone AUC in short time windows following each injection of RF9 and saline were comparable between the groups. Our results demonstrate that RF9 has no role in regulating HPG-axis under normal physiological conditions in adult male monkeys.


Endocrinology ◽  
1973 ◽  
Vol 92 (4) ◽  
pp. 1223-1228 ◽  
Author(s):  
A. BARTKE ◽  
R.E. STEELE ◽  
N. MUSTO ◽  
B.V. CALDWELL

1990 ◽  
Vol 70 (4) ◽  
pp. 1063-1072 ◽  
Author(s):  
R. D. H. COHEN ◽  
B. D. KING ◽  
L. R. THOMAS ◽  
E. D. JANZEN

Blood was collected at 0, 3, 6, 12, 24, 36 and 48 h postcastration and then daily for a further 6 d to determine the degree of stress following surgical or chemical castration (Chem-cast; α-hydroxypropionic acid) of Holstein calves. Stress indicators (plasma cortisol, packed cell volume, glucose, proteins, free fatty acids, creatinine, urea nitrogen and rectal temperature) were measured for all castrates and compared with entire bull calves. There were no effects on stress indicators except plasma cortisol. Plasma cortisol concentrations were significantly elevated at 3 and 6 h postcastration in castrated compared with in-tact cattle (P < 0.05). At these times, plasma cortisol concentrations in surgical castrates were greater than chemical castrates (P < 0.05). Greatest concentrations of cortisol were measured at 6 h following surgical castration (23.2 ± 0.64 μg L−1) and at 3 h following chemical castration (16.8 ± 0.49 μg L−1). Mean cortisol concentration in calves not castrated was 7.1 ± 0.26 μg L−1. From 12 h to 7 d postcastration, differences between groups for plasma cortisol were not significant. It was concluded that acute stress occurred for 6–12 h following castration and that surgical castration caused greater stress than chemical castration. There was an immediate decline in plasma testosterone levels in surgically castrated calves and these remained at undetectable levels throughout a 63-d postcastration period. Testosterone levels of chemically castrated calves declined immediately following the injection of Chem-cast but there was a gradual increase to, and long term maintenance of, low levels of testosterone which were greater than those of surgical castrates (P < 0.01) but less than those of entire males (P < 0.01). Palpation indicated severe testicular degeneration in chemically castrated males. The average daily gains (ADG) over the entire experimental period of 133 d did not differ between the entire males (1.1 ± 0.11 kg d−1) and surgical castrates (0.9 ± 0.05 kg d−1) or between the entire males and chemical castrates (1.2 ± 0.04 kg d−1) but ADG for chemical castrates was greater than that for surgical castrates (P < 0.05). Key words: Castration, Chem-cast®, stress, cattle, cortisol, testosterone


1974 ◽  
Vol 61 (2) ◽  
pp. 193-198 ◽  
Author(s):  
S. EL SAFOURY ◽  
A. BARTKE

SUMMARY The effects of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on plasma testosterone levels were examined in hypophysectomized and in intact immature and adult male rats. The animals were injected with saline, LH, FSH, or both gonadotrophins twice daily for 3·5 days and were killed 3 h after the last injection. Plasma testosterone levels were measured by radioimmunoassay. In immature hypophysectomized rats, plasma testosterone levels were not changed by treatment with LH, FSH or LH plus FSH. The weight of the testes and of the seminal vesicles was increased only in animals injected with both LH and FSH. In adult hypophysectomized rats, LH caused the expected increase in plasma testosterone levels, while FSH injected alone had no effect. Plasma testosterone levels in rats treated with 5 μg LH and 20 μg FSH were significantly greater than those in animals given 5 μg LH alone. However, the same dose of FSH did not potentiate the action of 25 μg LH on plasma testosterone levels. In adult hypophysectomized rats the weight of testes was not affected by any of the treatments. The weight of the seminal vesicles was increased by the higher dose of LH and addition of FSH caused no further increase. In intact immature and adult rats plasma testosterone levels and the weight of testes were not changed by any of the treatments. Seminal vesicle weight was increased only in adult rats treated with the higher dose of LH together with FSH. The results demonstrate that FSH potentiates the action of low doses of LH on plasma testosterone levels in adult hypophysectomized rats and suggest that FSH may be involved in the regulation of androgen secretion by the rat testis.


1978 ◽  
Vol 76 (1) ◽  
pp. 67-74 ◽  
Author(s):  
R. M. ROSE ◽  
T. P. GORDON ◽  
I. S. BERNSTEIN

SUMMARY Concentrations of cortisol and testosterone in the plasma of adult male rhesus monkeys living in social groups were determined during a 27-h period. Capture and venipuncture of experienced, conditioned animals did not lead to a fall in the concentration of testosterone in the plasma during the 90 min immediately after removal from the group. Both plasma cortisol and plasma testosterone concentrations showed a significant fall and rise in samples collected every 3 h during a 27-h period, even though there was considerable individual variation. During the autumn breeding season, animals showed higher concentrations of testosterone at both 10.00 and 22.00 h compared with those observed at the same times during the summer. Even though animals demonstrated significant diurnal changes, testosterone samples withdrawn at the same time of day (10.00 h) on consecutive days were significantly correlated with one another (r = 0·65, n = 27, P < 0·01), suggesting the usefulness of sampling once a day to study potential environmental influences on plasma testosterone concentrations.


1981 ◽  
Vol 59 (6) ◽  
pp. 1062-1066 ◽  
Author(s):  
L. Boissin-Agasse ◽  
D. Maurel ◽  
J. Boissin

Plasma thyroxine (T4) and testosterone concentrations were measured in adult male mink maintained outdoors under natural light and fed ad libitum the whole year round. Plasma T4 concentrations presented a biphasic seasonal change, the highest values occurring in the spring and autumn months and the lowest values in the winter months. The plasma testosterone cycle showed an annual maximum in January–February. The possibility of testis–thyroid interactions is discussed. The changes observed are correlated with environmental temperature, photoperiod, and molting cycle.


Science ◽  
1972 ◽  
Vol 178 (4061) ◽  
pp. 643-645 ◽  
Author(s):  
R. M. Rose ◽  
T. P. Gordon ◽  
I. S. Bernstein

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