scholarly journals Leptin inhibits testosterone secretion from adult rat testis in vitro

1999 ◽  
Vol 161 (2) ◽  
pp. 211-218 ◽  
Author(s):  
M Tena-Sempere ◽  
L Pinilla ◽  
LC Gonzalez ◽  
C Dieguez ◽  
FF Casanueva ◽  
...  
Keyword(s):  
Adult Male ◽  
Reproductive Function ◽  
Serum Testosterone ◽  
Testicular Tissue ◽  
Male Rats ◽  
Adult Males ◽  
Adult Rats ◽  
Adult Rat ◽  
Testosterone Secretion

Leptin, the product of the ob gene, has emerged recently as a pivotal signal in the regulation of fertility. Although the actions of leptin in the control of reproductive function are thought to be exerted mainly at the hypothalamic level, the potential direct effects of leptin at the pituitary and gonadal level have been poorly characterised. In the present study, we first assessed the ability of leptin to regulate testicular testosterone secretion in vitro. Secondly, we aimed to evaluate whether leptin can modulate basal gonadotrophin and prolactin (PRL) release by incubated hemi-pituitaries from fasted male rats. To attain the first goal, testicular slices from prepubertal and adult rats were incubated with increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Assuming that in vitro testicular responsiveness to leptin may be dependent on the background leptin levels, testicular tissue from both food-deprived and normally-fed animals was used. Furthermore, leptin modulation of stimulated testosterone secretion was evaluated by incubation of testicular samples with different doses of leptin in the presence of 10 IU human chorionic gonadotrophin (hCG). In addition, analysis of leptin actions on pituitary function was carried out using hemi-pituitaries from fasted adult male rats incubated in the presence of increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Serum testosterone levels, and basal and hCG-stimulated testosterone secretion by incubated testicular tissue were significantly decreased by fasting in prepubertal and adult male rats. However, a significant reduction in circulating LH levels was only evident in adult fasted rats. Doses of 10(-9)-10(-7) M leptin had no effect on basal or hCG-stimulated testosterone secretion by testes from prepubertal rats, regardless of the nutritional state of the donor animal. In contrast, leptin significantly decreased basal and hCG-induced testosterone secretion by testes from fasted and fed adult rats. In addition, 10(-9) M leptin inhibited LH and FSH secretion by incubated hemi-pituitaries from fasted adult males, whereas, at all doses tested, it was ineffective in modulating PRL release. Our results show that leptin, depending on the state of sexual maturation, is able to inhibit testosterone secretion acting at the testicular level. Furthermore, the present data suggest that the actions of leptin on the reproductive system are complex and are probably carried out at different levels of the hypothalamic-pituitary-gonadal axis.

scholarly journals In vitro pituitary and testicular effects of the leptin-related synthetic peptide leptin(116-130) amide involve actions both similar to and distinct from those of the native leptin molecule in the adult rat

2000 ◽  
pp. 406-410 ◽  
Author(s):  
M Tena-Sempere ◽  
L Pinilla ◽  
LC Gonzalez ◽  
J Navarro ◽  
C Dieguez ◽  
...  
Keyword(s):  
Body Weight ◽  
Adult Male ◽  
Body Weight Gain ◽  
Biologically Active ◽  
Male Rats ◽  
Male Rat ◽  
Gh Secretion ◽  
Adult Rat ◽  
Testosterone Secretion

The obese gene (ob) product, leptin, has recently emerged as a key element in body weight homeostasis, neuroendocrine function and fertility. Identification of biologically active, readily synthesized fragments of the leptin molecule has drawn considerable attention, as they may provide a powerful tool for detailed characterization of the biological actions of leptin in different experimental settings. Recently, a fragment of mouse leptin protein comprising amino acids 116-130, termed leptin(116-130) amide, was shown to mimic the effects of the native molecule in terms of body weight gain and food intake, and to elicit LH and prolactin (PRL) secretion in vivo. As a continuation of our previous experimental work, the present study reports on the effects of leptin(116-130) amide on basal and stimulated testosterone secretion by adult rat testis in vitro. In addition, a comparison of the effects of human recombinant leptin and leptin(116-130) amide at the pituitary level on the patterns of LH, FSH, PRL and GH secretion is presented. As reported previously by our group, human recombinant leptin(10(-9)-10(-7)M) significantly inhibited both basal and human chorionic gonadotrophin (hCG)-stimulated testosterone secretion in vitro. Similarly, incubation of testicular tissue in the presence of increasing concentrations of leptin(116-130) amide (10(-9)-10(-5)M) resulted in a dose-dependent inhibition of basal and hCG-stimulated testosterone secretion; a reduction that was significant from a dose of 10(-7)M upwards. In addition, leptin(116-130) amide, at all doses tested (10(-9)-10(-5)M), significantly decreased LH and FSH secretion by incubated hemi-pituitaries from adult male rats. In contrast, in the same experimental protocol, recombinant leptin(10(-9)-10(-7)M) was ineffective in modulating LH and FSH release. Finally, neither recombinant leptin nor leptin(116-130) amide were able to change basal PRL and GH secretion in vitro. Our results confirm the ability of leptin, acting at the testicular level, to inhibit testosterone secretion, and map the effect to a domain of the leptin molecule that lies between amino acid residues 116 and 130. In addition, we provide evidence for a direct inhibitory action of leptin(116-130) amide on pituitary LH and FSH secretion, a phenomenon not observed for the native leptin molecule, in the adult male rat.

EFFECT OF SEX AND AGE AT GONADECTOMY ON THE SEBACEOUS RESPONSE TO PROGESTERONE

1977 ◽  
Vol 73 (1) ◽  
pp. 67-70 ◽  
Author(s):  
SAM SHUSTER ◽  
WENDY M. HINKS ◽  
A. J. THODY
Keyword(s):  
Adult Female ◽  
Adult Male ◽  
Female Rats ◽  
Male Rats ◽  
Adult Males ◽  
Adult Rat ◽  
Sebum Production ◽  
Males And Females ◽  
Sebum Secretion

SUMMARY The effect of progesterone on the rate of sebum secretion was examined in intact and gonadectomized rats. In intact, adult, male rats, progesterone administered for 3 weeks decreased sebum secretion; after castration of adult males, progesterone increased sebum secretion and an even greater response occurred in males castrated at 21 days of age. In intact, adult, female rats progesterone slightly increased sebum production. As in the male, the response was affected by the time of gonadectomy, a greater response occurring after spaying at 21 days compared with 10 weeks of age. Thus, the response to progesterone in the adult rat differs in intact males and females and is affected by changes in the endocrine environment induced by gonadectomy, especially near the time of puberty.

Characterization of the reproductive effects of the anorexigenic VGF-derived peptide TLQP-21: in vivo and in vitro studies in male rats

2011 ◽  
Vol 300 (5) ◽  
pp. E837-E847 ◽  
Author(s):  
Leonor Pinilla ◽  
Rafael Pineda ◽  
Francisco Gaytán ◽  
Magdalena Romero ◽  
David García-Galiano ◽  
...  
Keyword(s):  
Chronic Administration ◽  
Testicular Tissue ◽  
Male Rats ◽  
Central Administration ◽  
Adult Males ◽  
Hpg Axis ◽  
Reproductive Effects

VGF (nonacronymic) is a 68-kDa protein encoded by the homonymous gene, which is expressed abundantly at the hypothalamus and has been involved in the control of metabolism and body weight homeostasis. Different active peptide fragments are generated from VGF, including TLQP-21. Circumstantial evidence has suggested that VGF might also participate in the control of reproduction. Yet its mechanisms of action and the eventual role of specific VGF-derived peptides on the hypothalamic-pituitary-gonadal (HPG) axis remain unknown. Herein we report a series of studies on the reproductive effects of TLQP-21 as evaluated in male rats by a combination of in vivo and in vitro analyses. Central administration of TLQP-21 induced acute gonadotropin responses in pubertal and adult male rats, likely via stimulation of GnRH secretion, as documented by static incubations of hypothalamic tissue. In addition, in pubertal (but not adult) males, TLQP-21 stimulated LH secretion directly at the pituitary level. Repeated central administration of TLQP-21 to pubertal males subjected to chronic undernutrition was able to ameliorate the hypogonadotropic state induced by food deprivation. In contrast, chronic administration of TLQP-21 to fed males at puberty resulted in partial desensitization and puberty delay. Finally, in adult (but not pubertal) males, TLQP-21 enhanced hCG-stimulated testosterone secretion by testicular tissue in vitro. In summary, our data are the first to document a complex and multifaceted mode of action of TLQP-21 at different levels of the male HPG axis with predominant stimulatory effects, thus providing a tenable basis for the (direct) reproductive role of this VGF-derived peptide.

The contribution of corticosterone and testosterone to the suppression of serum LH in hyperprolactinaemic adult male rats with pituitary transplants

1987 ◽  
Vol 113 (1) ◽  
pp. 111-116 ◽  
Author(s):  
R. F. A. Weber ◽  
M. P. Ooms ◽  
J. T. M. Vreeburg
Keyword(s):  
Adult Male ◽  
Serum Testosterone ◽  
Serum Levels ◽  
Male Rats ◽  
Male Rat ◽  
Serum Concentrations ◽  
Testosterone Secretion ◽  
Accessory Sex Glands ◽  
Serum Lh ◽  
Stimulation Of

ABSTRACT The effects of hyperprolactinaemia on serum levels of LH were investigated in adult male rats of the R × U strain. Hyperprolactinaemia was induced by three pituitary grafts under the kidney capsule, transplanted on day 0 of each experiment. Special attention was paid to the contribution of prolactin-stimulated testes, adrenals and corticosterone. In experiment 1, hyperprolactinaemia significantly reduced the serum concentrations of LH in intact rats. In spite of a significant increase in the serum levels of corticosterone, serum testosterone was not significantly affected by hyperprolactinaemia. The weights of both the adrenals and accessory sex glands were significantly increased at autopsy. In experiment 2, treatment with 10 mg corticosterone s.c. daily from day 14 to day 28 after pituitary grafting significantly reduced serum levels of both LH and testosterone. The suppression of testosterone in the hyperprolactinaemic corticosterone-treated animals was significantly less than in the corticosterone-treated control animals. The weights of the accessory sex glands were significantly increased in the hyperprolactinaemic animals. In experiment 3, rats were adrenalectomized and half of them were substituted with corticosterone. Serum testosterone levels significantly increased in both hyperprolactinaemic adrenalectomized rats and in adrenalectomized corticosterone-treated animals without any significant effect on serum LH. Again the weights of the accessory sex glands were significantly increased in the hyperprolactinaemic animals. In experiment 4, rats were adrenalectomized, gonadectomized and corticosterone treated on day 0 and then implanted with a 2, 1·5 or 1 cm silicone elastomer capsule containing testosterone. On day 28 after pituitary grafting, LH levels were significantly suppressed in animals with a 2 or 1·5 cm testosterone implant. The weights of the accessory sex glands were not increased in the hyperprolactinaemic animals. These results show that in the male rat the inhibitory effects of hyperprolactinaemia on serum LH levels may be due to (1) increased sensitivity of the hypothalamic-pituitary axis to the negative feedback action of testosterone by prolactin and by the prolactin-stimulated corticosterone secretion and (2) stimulation of testicular testosterone secretion by prolactin, which can also explain the increased weights of the accessory sex glands. Even in the presence of high serum concentrations of corticosterone, stimulation of testicular testosterone secretion by prolactin was observed. J. Endocr. (1987) 113,111–116

Reproductive toxicity and tissue concentrations of 3,3',4,4'-tetrachlorobiphenyl (PCB 77) in male adult rats

1998 ◽  
Vol 17 (3) ◽  
pp. 151-156 ◽  
Author(s):  
A S Faqi ◽  
P R Dalsenter ◽  
W Mathar ◽  
B Heinrich-Hirsch ◽  
I Chahoud
Keyword(s):  
Adult Male ◽  
Weight Control ◽  
Reproductive Toxicity ◽  
Serum Testosterone ◽  
Male Rats ◽  
Testis Weight ◽  
Adult Rats ◽  
Male Adult ◽  
Reproductive Effects ◽  
Investigation Period

1 The aim of this study was to ascertain the reproductive effects of PCB 77 on adult male rats and to determine its concentration in the liver and testis. Adult male rats (n=15/group) were treated subcutaneously with a singledoseof18 mg/kgbw(PC18)orwith60 mg/kg bw (PC60). The substance was dissolved in a 10 ml volume of peanut oil/kg. Control rats received the same volume of the vehicle. The reproductive effects as well as the concentration of PCB 77 in the liver and testis were investigated 1, 4 and 8 weeks after treatment. 2 In both groups, the daily sperm production (DSP; 6106) remained permanently reduced in the PC18 as well as in the PC60 groups throughout the entire investigation period (DSP week 8: control: 31+7; PC18: 22+5; PC60: 20+7). The sperm number (6106) per cauda epididymis was affected only at the 1st and 4th week after treatment (control week 1: 211+67; PC18 week 1: 135+62; PC60 week 1: 142+49). Moreover, a significant increase in the percentage of abnormal sperm was observed 4 weeks following treatment in the PC18 and PC60 groups and 8 weeks after treatment in the PC60 group. Abnormal tails were the most frequent changes observed. 3 The relative testicular and prostata weights (g) were slightly increased in the PC60 group at the 1st and 4th week following treatment (testis weight: control/I: 0.46+0.02; PC60/I: 0.51+0.03). 4 The serum testosterone concentrations and effects on testis morphology were not reported. 5 The maximum concentration of PCB 77 was detected in the liver and testis 1 week after treatment. The concentration declined 4 weeks after treatment in both organs, but still a significant amount of PCB 77 was detectable in the liver as well as in the testis 8 weeks after treatment. 6 The results demonstrate that PCB 77 affects sperm variables when applied to adult rats and that the elimination of PCB 77 in the testis parallels that of the liver.

Dependency of lactose absorption on lactase activity in starved rats

1987 ◽  
Vol 65 (11) ◽  
pp. 2287-2290 ◽  
Author(s):  
Joseph Leichter ◽  
Toshinao Goda ◽  
Otakar Koldovsky
Keyword(s):  
Adult Male ◽  
Specific Activity ◽  
Male Rats ◽  
Lactase Activity ◽  
Adult Rats ◽  
Enhanced Absorption

The effects of starvation on intestinal disaccharidase activities and disaccharide absorption were studied in rats. Adult male rats were starved for either 16 or 72 h and the specific activity of lactase and sucrase was determined together with the absorption of lactose, sucrose, and glucose in vitro by the everted sac technique. The specific activity of lactase was significantly higher and the specific activity of sucrase was lower in the 72-h starved animals when compared with the 16-h starved group. The higher specific lactase activity in the 72-h starved animals was reflected in enhanced absorption of lactose as determined by the transfer of the constituent monosaccharides into the serosal fluid. The transfer of glucose into the serosal fluid by the glucose sac was also higher in the 72-h starved rats but not to the same extent as that of lactose. The absorption of sucrose was not significantly different between the two groups of animals. This study shows that the increase of intestinal lactase activity induced by starvation of adult rats correlates with in vitro increased lactose absorption.

Effects of hypophysectomy and subsequent FSH and testosterone treatment on inhibin production by adult rat testes

1985 ◽  
Vol 105 (1) ◽  
pp. 1-6 ◽  
Author(s):  
C. L. Au ◽  
D. M. Robertson ◽  
D. M. de Kretser
Keyword(s):  
Seminiferous Tubule ◽  
Hormonal Control ◽  
Human Chorionic Gonadotrophin ◽  
Experimental Conditions ◽  
Adult Rats ◽  
Adult Rat ◽  
Fluid Production ◽  
Tubule Fluid

ABSTRACT The hormonal control of inhibin production by adult rat testes was investigated using an in-vitro inhibin bioassay validated for the measurement of inhibin activity in charcoal-treated rat testicular extracts. The effect of hypophysectomy examined at 16 h, 3, 7 and 42 days after surgery showed a decrease in testicular inhibin content and seminiferous tubule fluid production by 7 days and a decrease in inhibin production by 42 days. Serum FSH and LH were suppressed 3 days after surgery. In 30-day chronically hypophysectomized adult rats treated for 3 days with twice daily s.c. injections of (a) human FSH (hFSH, 22 i.u./rat per day), (b) testosterone (5 mg/rat per day), (c) hFSH + testosterone (same doses as a and b), or (d) human chorionic gonadotrophin (hCG, 12 i.u./rat per day), hFSH or hFSH and testosterone stimulated an increase in testicular inhibin content but not in inhibin production or tubule fluid production. Testosterone and hCG had no effect on these parameters. It is concluded that in vivo, FSH alone stimulates an increase in testicular inhibin content. The failure to observe an increase in inhibin production in vivo is attributed to the suppression of seminiferous tubule fluid production under the same experimental conditions. J. Endocr. (1985) 105, 1–6

Selective Modulation of Tonic and Phasic Inhibitions in Dentate Gyrus Granule Cells

2002 ◽  
Vol 87 (5) ◽  
pp. 2624-2628 ◽  
Author(s):  
Zoltan Nusser ◽  
Istvan Mody
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Hippocampal Slices ◽  
Tonic Inhibition ◽  
Adult Rats ◽  
Adult Rat ◽  
Phasic Inhibition ◽  
The Mean

In some nerve cells, activation of GABAA receptors by GABA results in phasic and tonic conductances. Transient activation of synaptic receptors generates phasic inhibition, whereas tonic inhibition originates from GABA acting on extrasynaptic receptors, like in cerebellar granule cells, where it is thought to result from the activation of extrasynaptic GABAA receptors with a specific subunit composition (α6βxδ). Here we show that in adult rat hippocampal slices, extracellular GABA levels are sufficiently high to generate a powerful tonic inhibition in δ subunit–expressing dentate gyrus granule cells. In these cells, the mean tonic current is approximately four times larger than that produced by spontaneous synaptic currents occurring at a frequency of ∼10 Hz. Antagonizing the GABA transporter GAT-1 with NO-711 (2.5 μM) selectively enhanced tonic inhibition by 330% without affecting the phasic component. In contrast, by prolonging the decay of inhibitory postsynaptic currents (IPSCs), the benzodiazepine agonist zolpidem (0.5 μM) augmented phasic inhibition by 66%, while leaving the mean tonic conductance unchanged. These results demonstrate that a tonic GABAA receptor–mediated conductance can be recorded from dentate gyrus granule cells of adult rats in in vitro slice preparations. Furthermore, we have identified distinct pharmacological tools to selectively modify tonic and phasic inhibitions, allowing future studies to investigate their specific roles in neuronal function.

Metabolic Studies on the Mechanisms of Increased Susceptibility of Weanling Rats to Parathion

1972 ◽  
Vol 50 (9) ◽  
pp. 902-915 ◽  
Author(s):  
Jacques Gagné ◽  
Jules Brodeur
Keyword(s):  
Toxic Effects ◽  
Intravenous Route ◽  
Toxic Metabolite ◽  
Adult Males ◽  
Adult Rats ◽  
Renal Handling ◽  
Weanling Rats ◽  
The Brain ◽  
Increased Susceptibility

Equitoxic doses of 32P-parathion (1.5 mg/kg in weanlings of both sexes, 2.0 mg/kg in adult females, and 3.1 mg/kg in adult males) were given by the intravenous route to immature and adult rats in order to investigate the respective contribution of biotransformation, distribution, and excretion phenomena to the increased susceptibility of weanling rats to the acute toxic effects of parathion. At various intervals, the animals were sacrified and the amounts of parathion, paraoxon, diethylphosphorothioic acid, and diethylphosphoric acid in the liver, kidneys, tibial muscle, plasma, brain, adipose tissue, and urine were determined. In vitro metabolism of 32P-parathion by liver homogenates was also investigated. The results obtained suggest that weanlings are more susceptible to parathion than adults mainly because of deficient hepatic mechanisms for degradation of parathion and its toxic metabolite, paraoxon. In addition, the brain tissue of weanlings appears to be more sensitive to the toxic effects of paraoxon than the brain of male adults. On the other hand, the passage of parathion and paraoxon across the blood–brain barrier does not seem to be facilitated in weanlings by comparison with adults. Finally, there is no evidence that the renal handling of parathion and its metabolites might influence the acute toxicity of parathion in weanling and adult rats.

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