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Biomedical subjects

I Gerendai

Publications and source records attributed to I Gerendai.

At least 19 recordsLinked to original sources

Vasectomy modulates the local effect of intratesticular opioids on the gonad of immature rats.

Previous studies indicate that 7 days after testicular administration of naloxone, serum testosterone (T) concentration and basal T secretion in vitro decrease significantly. In neonatal rats, short-term (2 h) intratesticular treatment with 0.3 micrograms (D-Met2-Pro5)-enkephalinamide suppresses steroidogenesis. In the present study, testicular treatment with naloxone or enkephalinamide was combined with hemivasectomy (which also includes transection of the inferior spermatic nerve). When local treatment with naloxone was combined with vasectomy in 15-day-old rats, the opioid antagonist-induced increase in testicular weight, the decrease in basal T secretion of the treated gonad and the drop in serum T level could not be observed 7 days postsurgery, despite the fact that in immature rats, hemivasectomy, by itself, also reduces steroid secretion. Similarly, in 5-day-old animals, the short-term (2 h) effect of testicular enkephalinamide on T secretion was prevented by vasectomy. These data suggest that local testicular actions exerted by endogenous opioid peptides might be modulated by the inferior spermatic nerve.

Animals

Modulation of testicular functions by testicular opioid peptides.

The possible physiological role of testicular opioid peptides in the control of testicular functions has been studied. In neonatal rats intratesticular administration of opiate receptor antagonists (naloxone, nalmefene) stimulates Sertoli cell proliferation and secretion. Both in adult and neonatal rats local injection of the testis with opiate receptor antagonists or with beta-endorphin antiserum results in a decrease in steroidogenesis in long-term studies. Treatment of neonatal testis with an enkephalin analogue induces a short-term suppression of testosterone secretion. Further studies were carried out to investigate whether the above described local effects of opiate agonist or antagonist on testicular function are under the regulatory control of testicular nerves. Partial denervation of the testis was performed by testicular injection of 6-hydroxydopamine (a neurotoxin degenerating sympathetic neural structures) or by vasectomy (cutting the inferior spermatic nerve). If testicular administration of opioid agonist or antagonist was combined with partial denervation of the testis, the effects of pharmacological agents influencing testicular opioid level were not evident. The data indicate that opioid peptides synthesized in the testis are components of the intratesticular regulatory system and that local opioid actions are modulated by testicular nerves.

Animals

Intratesticular injection of [D-Met2-Pro5]enkephalinamide suppresses testosterone secretion of the testis of immature rat.

The possible role of enkephalin in the local control of testicular function was studied in neonatal rats. 5- and 10-day old hemicastrated rats were treated intratesticularly with an enkephalin analog [D-Met2-Pro5]enkephalinamide. In 5-day-old rats local injection of different doses (0.1-0.3 micrograms/testis) of the peptide suppressed basal testosterone secretion in vitro in a dose-dependent manner 2 h posttreatment. Intratesticular administration of naloxone prior to enkephalin treatment prevented the decrease in basal testosterone production induced by the opioid agonist. In 10-day-old animals intratesticular injection of 1.0 and 3.0 micrograms/testis of enkephalinamide reduced serum testosterone concentration and basal testosterone secretion in vitro. Systemic injection of the peptide produced no change in steroidogenesis. These results suggest that enkephalins might be among the intratesticular factors regulating Leydig cell functions.

Animals

Effect of unilateral vagotomy on serum gonadotropin concentration in rats with two testes and in hemicastrates.

The effect of right- or left-sided vagotomy on serum gonadotropin secretion was studied in rats with two testes and in hemicastrates. Right-sided vagotomy in animals with two testes in situ induced a very marked rise in serum LH levels. Left-sided vagotomy was also accompanied with a slight increase in LH secretion. The difference in serum LH levels between right-and left-sided vagotomized animals was significant. FSH levels were unaffected by either right- or left-sided vagotomy. Removal of the right or of the left testis resulted in a significant increase in serum gonadotropin levels. Unilateral vagotomy in hemicastrates did not alter the hemicastration-induced changes in serum gonadotropin hormone levels. These data indicate that the vagus nerve might have a modulatory role in the control of LH secretion in rats with two testes but not in hemicastrates. The different response in LH levels after right-sided and left-sided vagotomy suggests a functional asymmetry of the vagus nerve in the regulation of LH secretion.

Animals

The effects of opioid receptor antagonists suggest that testicular opiates regulate Sertoli and Leydig cell function in the neonatal rat.

beta-Endorphin and other peptides derived from proopiomelanocortin are synthesized in testicular Leydig cells. To better understand the possible function of these and other endogenous opioid peptides in the testis, the opioid antagonists naloxone and nalmefene were administered intratesticularly to hemicastrated 5-day-old rats. Both naloxone and nalmefene potentiated testicular hypertrophy induced by unilateral orchidectomy at 11 days of age. Unexpectedly, at least a 100-fold lower dose of nalmefene was required to produce maximal hypertrophy than that previously reported for naloxone. Leydig and Sertoli cell functions were evaluated, respectively, by measurement of basal testosterone production in vitro and rat androgen-binding protein (rABP) in serum. The optimal dose of naloxone for hypertrophy (1 microgram/testis) suppressed testosterone production and had a nonuniform effect on rABP secretion (either had no effect or produced a slight increase). By contrast, the optimal dose of nalmefene for hypertrophy (0.01 microgram/testis) not only suppressed basal testosterone secretion, but also uniformly increased rABP levels in serum. Larger doses of this opioid antagonist, up to 1 microgram/testis, were not as effective on the three parameters measured (hypertrophy, testosterone secretion, and rABP levels). These results suggest that this agent has both antagonistic and agonistic activities in the testis. At the doses that produced optimal effects on hypertrophy, systemic administration of these antagonists produced no effects. The results of these studies suggest that intratesticular opiates exert a suppressive effect on Sertoli cell growth and rABP secretion. In addition, these peptides may modulate testosterone secretion by Leydig cells.

Androgen-Binding Protein

Pro-opiomelanocortin-derived peptides in the testis: evidence for a possible role in Leydig and Sertoli cell function.

Pro-opiomelanocortin (POMC)-derived peptides such as beta-endorphin, ACTH, and MSHs were identified in the testis where they were exclusively localized in Leydig cells. Examination of testicular extracts by a variety of physicochemical and immunological techniques indicates that the processing of the POMC in the testis is very similar to that in the brain. By using a cDNA probe, the POMC-like mRNA present in total testis and cultured Leydig cells was 150-200 bases shorter than that in the hypothalamus and pituitary. In addition, POMC mRNA was localized to Leydig cells using in situ hybridization. The expression of the POMC-like gene and the accumulation of POMC-derived peptides in Leydig cell were shown to be under the control of gonadotropin. As the testis contains low concentrations of POMC-derived peptides, we suggested that they may be implicated in local regulatory events within this organ. This postulate was supported by results from in vivo and in vitro experiments suggesting that different portions of the POMC-molecule may have opposite effects on Sertoli cell functions. For example, MSHs increased cAMP accumulation and aromatase activity in these cells, while opioids inhibited Sertoli cell proliferation and androgen binding protein (ABP) secretion. Furthermore, following intratesticular administration of opiate antagonists, testosterone production was reduced, suggesting that Leydig cell function may be also modulated by beta-endorphin and/or other related peptides. Taken together, these studies support the hypothesis of a possible role of POMC-derived peptides in testicular function.

Animals

Unilateral vagotomy inhibits compensatory kidney growth after unilateral nephrectomy in rats.

The effect of unilateral vagotomy on compensatory renal growth that follows unilateral nephrectomy was studied. Unilateral vagotomy inhibited the usual compensatory growth of the remaining kidney. Unilateral vagotomy did not effect kidney weight in animals with two kidneys. Data indicate that the vagus nerve is involved in the development of compensatory kidney hypertrophy.

Animals

Effect of unilateral or bilateral thyroidectomy on TRH content of hypothalamus halves.

The effect of uni- or bilateral thyroidectomy on the thyrotropin-releasing hormone (TRH) content of the mediobasal hypothalamus (MBH) of the two sides was studied in male rats. Both right- and left-side hemithyroidectomy resulted in a significantly increased TRH content in both halves of the MBH. In addition, the total TRH content rise of the MBH was higher after unilateral than after bilateral thyroidectomy. The mechanism of action of uni- or bilateral thyroidectomy on the hypothalamic TRH content is discussed.

Animals

Effects of mastectomy and vagotomy on grooming behavior of the rat: possible involvement of prolactin.

Surgical interventions such as unilateral mastectomy or vagotomy affect plasma prolactin (PRL) levels. Right-side mastectomized rats exhibiting high levels of plasma PRL showed increased grooming behavior. Left-side mastectomized rats with low levels of plasma PRL performed poor grooming activity. Bilateral mastectomy that caused a slight increase in plasma PRL levels was followed by enhanced grooming behavior. Both left and right vagotomy resulted in a significant increase in plasma PRL levels. However, only left-side vagotomized rats exhibited increased levels of grooming behavior, while no difference between right-side vagotomized rats and controls occurred. It is possible that changes in plasma PRL levels induced by surgical interventions affect grooming activity of the rat. However, the hypothesis that the integrity of peripheral organs is important for the display of grooming behavior cannot be ruled out.

Animals

Depending on the dose 6-OHDA stimulates or inhibits the testis of immature rats.

The effect of the neurotoxic drug, 6-hydroxy-dopamine (6-OHDA) on the testicular growth, the compensatory testicular hypertrophy, the testicular cytology and the serum testosterone level was studied in immature rats. Unilateral injection of 33 micrograms of 6-OHDA beneath the testicular capsule in animals with two testes did not alter the weight of the gonads but promoted the development of both testes. Unilateral injection of 333 micrograms of 6-OHDA resulted in a decreased weight and severe atrophy of the treated gonad, while a significant weight gain of the contralateral testis occurred. In hemicastrated rats 33 micrograms of 6-OHDA into the remaining testis caused an enhanced compensatory testicular hypertrophy. When 333 micrograms of 6-OHDA was administered beneath the capsule of the remaining testis a diminished compensatory testicular hypertrophy occurred but no signs of degeneration could be observed. Data indicate that the testicular adrenergic elements play a role in the testicular growth, in the development of compensatory testicular hypertrophy and in the cytodifferentiation of the immature testis.

Animals

Identification and possible function of pro-opiomelanocortin-derived peptides in the testis.

Using antibodies against peptides derived from different portions of the POMC molecule, immunocytochemical evidence suggests that this precursor and/or the peptides present within it are localized in testicular Leydig cells of at least five species. There is no evidence for the localization of these peptides or their precursor in any other cell type in this organ. Examination of testicular extracts by gel filtration, SDS-PAGE, and RP-HPLC indicate that the testis contains low concentrations of POMC-derived peptides relative to brain. Further analysis indicates that POMC is processed to alpha-MSH and beta-endorphin similar to its processing in intermediate pituitary lobe and brain. The relative mobilities of immunoreactive alpha-MSH and beta-endorphin on RP-HPLC columns indicate that they are in the unacetylated state as in brain and in contrast to the acetylated forms in the intermediate pituitary lobe. The potential for Leydig cells to synthesize POMC and its peptides was suggested by the demonstration of POMC-like mRNA in total testis and Leydig cell cultures. The size of the POMC-like mRNA is approximately 150 base pairs shorter than anterior or intermediate pituitary POMC mRNA. POMC-like mRNA activity has also been localized to Leydig cells in sections of testes using in situ hybridization. Immunostainable beta-endorphin and other POMC-derived peptides are present in testicular Leydig cells during fetal life and following puberty at times when testosterone secretion is maximal. The accumulation of immunostainable POMC-derived peptides in Leydig cells is dramatically increased by LH and hCG. A variety of observations suggests that testicular cells can respond to POMC-derived peptides. ACTH and the MSHs stimulate growth and cAMP accumulation in Sertoli cells. By contrast, studies using antagonists suggested that beta-endorphin and/or another testicular opioid inhibit Sertoli cell proliferation and ABP secretion. These observations are consistent with the postulate that different portions of the POMC molecule may have opposite effects on Sertoli cell function and suggest a mechanism by which Leydig cells could modulate Sertoli cell activity. Intratesticular administration of opiate antagonists inhibits testosterone secretion both in vivo and in vitro. These observations suggest that Leydig cell-derived beta-endorphin may facilitate testosterone secretion either directly or indirectly. The finding of POMC and its derivative peptides in testis, ovary, adrenal, and placenta suggests that all steroid hormone-secreting organs in mammals may utilize this peptidergic system.

Adrenocorticotropic Hormone

Do testicular opiates regulate Leydig cell function?

beta-Endorphin is believed to be synthesized in testicular Leydig cells. To gain more information about the role of this and other endogenous opioid peptides in the testis, opiate antagonists (naloxone and nalmefene, 100 micrograms/testis) were administered intratesticularly to hemicastrated adult rats. Leydig cell function was evaluated by measurement of serum testosterone and testosterone production in vitro. Estimation of androgen binding protein (rABP) was used as an index of Sertoli cell function. Serum testosterone was reduced significantly by intratesticular administration of naloxone and nalmefene in treated animals. Systemic administration of these antagonists had no effect at the doses used. Testes from treated animals incubated in vitro with or without hCG produced significantly less testosterone than vehicle-treated control testes. Hemicastration reduced rABP synthesis and secretion; however, treatment with opiate antagonists did not alter the amount of this protein in the serum or epididymides of these rats. These observations suggest that endogenous testicular opiates modulate testosterone secretion by Leydig cells.

Androgen-Binding Protein

Unilateral posterior deafferentation of hypothalamus and mitotic activity of thyroid follicular cells under normal conditions and after hemithyroidectomy.

The effect of unilateral posterior deafferentation of the hypothalamus on the mitotic activity of thyroid follicular cells was studied in hemithyroidectomized and sham-operated rats. Left side posterior deafferentation of the hypothalamus reduced significantly the basal mitotic activity of both thyroid lobes and prevented the hemithyroidectomy-induced increase in mitotic activity of the remaining thyroid lobe. Right side posterior deafferentation of the hypothalamus or sham operation did not interfere with the normal or stimulated activity of the follicular cells. These data suggest left side dominance in the mitosis control of the thyroid cells but the mechanism resulting in these findings remains unclear.

Afferent Pathways

Increase in the LHRH content of the organum vasculosum of the lamina terminalis and the medio-basal hypothalamus six hours after injection of kainic acid into the rat medial preoptic area.

The luteinizing hormone-releasing hormone (LHRH) content of the organum vasculosum of the lamina terminalis (OVLT) and that of the medio-basal hypothalamus (MBH) was studied 6 h after the injection of 1 microgram of kainic acid into the medial preoptic area (MPOA) at the day of diestrus. The injection resulted in a highly elevated LHRH content in the OVLT which exceeded that of the controls observed on the afternoon of proestrus. LHRH content in the MBH increased significantly, however, it did not reach the peak value of proestrus. No change occurred in luteinizing hormone (LH) and prolactin (PRL) levels, while serum follicle-stimulating hormone (FSH) values decreased significantly. The increased LHRH content of the OVLT and of the MBH might be due to an enhanced LHRH synthesis and/or to the stimulation of neurons which inhibit LHRH release.

Animals

Less severe ovarian atrophy in hypophysectomized hemiovariectomized rats than in hypophysectomized animals with two ovaries.

The effect of unilateral ovariectomy (OVX) on the weight of the remaining ovary was studied in hypophysectomized (HYPOX) rats. 2 weeks following hypophysectomy + unilateral OVX the weight loss of the ovary is significantly less than that in HYPOX rats having two ovaries. Present data together with previous findings suggest that a neural pathway between the ovaries and the CNS may be involved in the mechanism of compensatory ovarian hypertrophy following removal of one ovary.

Animals