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Endocrine secretions under abnormal light-dark cycles and in the blind.

Both endogenous and exogenous factors are involved in regulation of endocrine secretions. Among the exogenous ones, light plays an important role both in animals and in humans. Pineal gland mediates light action on the endocrine system, by means of variations of melatonin (MT) secretion. Here we discuss about the influence of abnormal light-dark cycles and in particular of blindness on pineal and pituitary secretions and on those of correlated glands. MT secretion is usually inhibited by light: thus it reaches the highest levels at night. Exposure to short or long photoperiod causes variations in circadian or infradian MT rhythmicity. Blind patients can show higher daytime levels with a phase-advanced or phase-delayed circadian rhythm. Lack of light stimulus affects cortisol rhythm shifting the zenith of secretion and inducing a free-running rhythm. Blindness can abolish nocturnal growth hormone (GH) peak and impair the GH response to some stimuli; moreover it impairs the growth of affected patients. Light stimulus influences favorably gonadal function both in animals and in man. In animals, sexual activity and gonadal function decline during the seasons with reduced luminosity. A similar finding has been described in women living in a region with a strong seasonal contrast in luminosity. Blindness can impair luteinizing hormone, follicle-stimulating hormone, prolactin and testosterone secretion in prepubertal boys causing pubertal delay or more severe hypogonadism; it can affect pubertal development and fertility in women. Light can influence thyroid function in animals. Lack of light stimulus in blind man seems to cause different effects on thyroid function before and after puberty. Increase of free thyroid hormone levels has been found in prepubertal but not in adult blind patients, probably due to a resetting of the threshold for thyrotropin feedback suppression after puberty in these patients.

Animals↗

The gonadal axis in men with schizophrenia.

The typical onset of schizophrenia during late adolescence and early adulthood has stimulated interest in the potential contribution of hypothalamo-pituitary-gonadal (HPG) axis abnormalities to this disorder. Previous investigations of reproductive hormone function in men with schizophrenia suggest diminished activity of the HPG axis. These studies have been hampered, however, by methodologic limitations. We have attempted to address these limitations by rigorous determination of gonadotropin and gonadal hormone levels, and attention to demographic and diagnostic variables. In contrast to prior studies, our results indicate that schizophrenic patients do not show statistically significant differences from healthy volunteers with respect to luteinizing hormone pulsatility, response to gonadotropin-releasing hormone challenge, and testosterone secretion. Due to the small number of subjects, however, these findings must be regarded as preliminary and warrant further study.

Adult↗

The clinical implications of the difference between castration, gonadotrophin releasing-hormone (GnRH) antagonists and agonist treatment on the morphology and expression of GnRH receptors in the rat ventral prostate.

OBJECTIVE: To examine the effects of castration and continuous gonadotrophin releasing-hormone (GnRH) agonist and antagonist therapy on the expression of GnRH-receptors type I (GnRH-RI) in rat ventral prostate (VP) and pituitary tissue, and to compare the effects on prostate morphology. MATERIAL AND METHODS: Mature Sprague-Dawley rats were assigned to four treatment groups: group 1, vehicle only; group 2, GnRH agonist goserelin (100 microg/rat/day); group 3, GnRH antagonist cetrorelix (100 microg/rat/day); and group 4, orchidectomy. After 4 weeks the body weights were recorded and VP and pituitary tissue analysed for GnRH-RI expression using a competitive reverse transcriptase-polymerase chain reaction and immunohistochemistry. RESULTS: GnRH antagonist and orchidectomy decreased testosterone secretion and VP volume similarly, but the effects were not identical. The involution of the glandular lumina was more pronounced after orchidectomy while the antagonist therapy was more effective in suppressing epithelial cell proliferation. In the VP, GnRH-RI mRNA levels were increased after GnRH analogue therapy, but were unaffected by orchidectomy. In the pituitary, GnRH-RI mRNA expression was higher in response to orchidectomy and decreased after GnRH analogue treatment. CONCLUSION: Treatment with a GnRH antagonist for 4 weeks is more effective than an agonist in suppressing testosterone and inducing VP involution. The GnRH antagonist was more effective in suppressing VP epithelial cell proliferation than was castration, suggesting that it induces reduced proliferation by interfering with effects of locally produced GnRH. These results suggest that different regulatory mechanisms may operate in the rat VP than in the pituitary to control GnRH-RI mRNA expression.

Animals↗

The effect of heavy resistance exercise on the circadian rhythm of salivary testosterone in men.

Circadian rhythms of serum testosterone concentrations in men have been shown, in general, to be highest in the morning and lowest in the evening. Thus, the purpose of this investigation was to determine the effects of acute resistance exercise upon the waking circadian rhythm of salivary testosterone over 2 days (with or without resistance exercise). The subjects included ten resistance-trained men (with at least 1 year of lifting experience) with the following characteristics [mean (SD)]: age 21.6 (1.1) years; height 177.8 (9.5) cm; body mass 80.5 (11.5) kg; percent body fat 7.9 (1.7)%. A matched, randomized, crossover study design was used such that each subject was tested under both the resistance exercise and control (no exercise) conditions. The resistance exercise protocol consisted of ten exercises performed for three sets of ten repetitions maximum with 2 min of rest between sets. Saliva sample 1 was collected at 0615 hours and resistance exercise began immediately afterwards at approximately 0620 hours, and sample 2 was collected at 0700 hours, which corresponded approximately to a mid-exercise (or control) time point. Saliva samples were then obtained every hour on the hour from 0800 hours until 2200 hours. No significant differences were observed between the exercise and resting conditions for salivary testosterone, with the exception of a significant decrease at 0700 hours during the resistance exercise protocol. The results of this investigation indicate that resistance exercise does not affect the circadian pattern of salivary testosterone secretion over a 16-h waking period in resistance-trained men.

Adult↗

Reduction in testicular function in rats. II. Reduction by dexamethasone in fetal and neonatal rats.

Chronic administration of dexamethasone in drinking water to maternal rats from days 15 to 21 of gestation (1) reduced plasma testosterone concentrations in male fetuses between days 19 and 21 but not earlier on day 18 and abolished the prenatal peak of plasma testosterone which normally occurs on day 19 of gestation, and (2) suppressed the postnatal surge of plasma testosterone in male newborns 1.5 and 2 h after delivery at term by cesarean section. The administration of dexamethasone to male fetuses at birth induced 1 h later a slight but not significant increase in hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary luteinizing hormone (LH) contents, reduced drastically plasma LH levels and completely prevented the postnatal surge of plasma testosterone which occurred normally in littermate controls. A rise in pituitary LH content, and a sharp reduction in plasma LH and testosterone concentrations were noted in 19-day-old male fetuses whose mothers were acutely treated with dexamethasone on day 18 of gestation. Similar evolutions for LH were observed in littermate females. These results suggest that the inhibitory effects of exogenous glucocorticoids on testosterone secretion could be mediated in both fetuses and newborns at least partially through suppression of the hypothalamic and pituitary secretion of GnRH and LH, respectively, and provide insight how stress or hormone imbalance may affect the development of this neuroendocrine system.

Animals↗

Cytoplasmic malic enzyme and testicular steroidogenesis in mice.

The malate shuttle has been hypothesized as a source of the intramitochondrial NADPH required for cholesterol side-chain cleavage. In the present report, the role of the malate shuttle in testicular steroidogenesis was investigated by employing mouse mutants deficient in cytoplasmic malic enzyme, a required component of the shuttle. Androgen-dependent parameters plus testosterone secretion by in vitro perfused testes were similar for the mutants and their normal siblings. The data suggest that an active malate shuttle is not required for cholesterol side-chain cleavage in mouse testes.

Animals↗

Adrenal-pituitary-gonadal relationships and ejaculate characteristics in captive leopards (Panthera pardus kotiya) isolated on the island of Sri Lanka.

In Study 1, semen was collected using a standardized electroejaculation procedure. Males (N = 8) produced ejaculates with a high incidence of sperm abnormalities (77 +/- 3.3%). After electroejaculation under anaesthesia, serum cortisol concentrations increased (P less than 0.05), while testosterone concentrations decreased (P less than 0.05) and LH and FSH concentrations were unchanged (P less than 0.05) over a 2-h bleeding period. In Study 2, male and female leopards were bled at 5-min intervals for 3 h and given (i.v.): (1) saline (N = 2/sex); (2) GnRH (1 microgram/kg body weight) 30 min after the onset of sampling (N = 5/sex); or (3) ACTH (250 micrograms) at 30 min followed by GnRH 1 h later (N = 5/sex). Basal concentrations of serum LH, FSH and cortisol were comparable (P greater than 0.05) between male and female leopards. After GnRH, peak LH concentrations were 2-fold greater (P less than 0.05) in males than females while FSH responses were similar. In males, testosterone concentrations increased 2-3-fold following GnRH. After ACTH, serum cortisol concentrations doubled within 15 min in both sexes. Administration of ACTH 1 h before GnRH did not affect GnRH-induced LH or FSH release (P greater than 0.05); however, testosterone secretion was only 30% of that observed after GnRH alone (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

LH-RH antagonist inhibits gonadal steroid secretion in vitro.

This investigation was aimed at studying the direct action of LH-RH derivatives on gonadal function. Modulation by LH-RH antagonist (Ac-[D-beta-Nal1, D-p-Cl-Phe2, D-Trp3, D-Arg6, D-Ala10]-LH-RH) and agonist of LH-RH (D-Ser(TBU)6, AzaGly10-LH-RH) and native LH-RH of HCG-stimulated steroidogenesis in testicular Leydig cells and luteal cells was studied in vitro. The LH-RH antagonist (3.2 X 10(-8) M) was found to change ED50 of HCG from 2 X 10(-11) M to 5.5 X 10(-11) M in the Leydig cell culture system. In addition, the antagonist was noted to override the stimulatory action of native LH-RH in Leydig cells. Furthermore, the agonist was found to augment HCG-provoked testosterone secretion. Similarly, the LH-RH antagonist at 10(-9) M blunted HCG-stimulated progesterone secretion in the luteal cell culture system and increased the ED50 of HCG from 8.7 X 10(-13) to 7.7 X 10(-12) M. In contrast to the Leydig cell culture system native LH-RH (10(-8) M) and the agonist (10(-8) M) increased the ED50 of HCG in luteal cells from 8.7 X 10(-13) M to 3 X 10(-12) M and 2.3 X 10(-12) M, respectively. Present data combine to suggest that LH-RH antagonists act at least partially at the gonadal level and may be clinically useful to inhibit Leydig cell and ovarian function.

Animals↗

Gonadotropin-releasing hormone analogues for prostate cancer: untoward side effects of high-dose regimens acquire a therapeutical dimension.

Gonadotropin-releasing hormone (Gn-RH), a hypothalamic decapeptide, mediates the synthesis and release of pituitary luteinizing hormone (LH). Synthetic Gn-RH analogues with prolonged duration of action are therapeutically administered with 'pro-fertility' intention to overcome endogenous Gn-RH deficiency, i.e. hypogonadotropic hypogonadism and related disorders. When Gn-RH analogues are chronically administered in high supraphysiological dosages, however, a paradoxical effect of pituitary overstimulation becomes evident: gonadotropin release is reduced, Leydig cell responsiveness is impaired, and testosterone secretion is blocked to castrate levels. Metabolic mechanisms involved include desensitization of the pituitary to Gn-RH, down-regulation of Gn-RH receptors, the depletion of the releasable LH pool, the breakdown of physiological feedback mechanisms, as well as direct interactions of the Gn-RH analogue with the Leydig cell. It is tempting to assume that, on the basis of this untoward side effect, high dose Gn-RH analogues will acquire a therapeutical dimension in the palliative treatment of prostate cancer. The therapeutical effect of castrate levels of testosterone is achieved without orchiectomy, cardiovascular side effects of estrogen are avoided, and the drug is conveniently applicable via the pernasal route. From the data available today Gn-RH analogues in overstimulatory dosage can be expected to be safe and effective in the palliative treatment of prostate cancer and would thus prove a true alternative to conventional contrasexual measures.

Adolescent↗

Serum dioxin-like activity is associated with reproductive parameters in young men from the general Flemish population.

BACKGROUND: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and some related environmental contaminants are aryl hydrocarbon receptor (AhR) ligands that exert reproductive and developmental toxicity in laboratory animals. In humans, fertility-related effects are less documented. OBJECTIVE: The aim of this study was to investigate the relationship between dioxin-like biological activity in serum and parameters of reproductive status in men from the general population 5 months after a polychlorinated biphenyl and dioxin food-contamination episode in Belgium. DESIGN: In the framework of the cross-sectional Flemish Environment and Health Study (FLEHS), we recruited 101 men 20-40 years of age and evaluated sperm parameters, measured sex hormones, and gathered information on a number of lifestyle factors. In addition, we determined the AhR-mediated enzymatic response elicited by individual serum samples and expressed it as TCDD equivalent concentrations (CALUX-TEQs) using an established transactivation assay. RESULTS: Age (p = 0.04) and the frequency of fish (p = 0.02) and egg (p = 0.001) consumption were independent positive determinants of serum dioxin-like activity. After correcting for possible confounders, we found that a 2-fold increase in CALUX-TEQ > 16 pg/L was associated with a 7.1% and 6.8% (both p = 0.04) decrease in total and free testosterone, respectively. We also observed a more pronounced drop in semen volume of 16.0% (p = 0.03), whereas sperm concentration rose by 25.2% (p = 0.07). No relationship was found with total sperm count or sperm morphology. CONCLUSIONS: These data suggest an interaction of dioxin-like compounds with the secretory function of the seminal vesicles or prostate, possibly indirectly through an effect on testosterone secretion, at levels not affecting spermatogenesis as such.

Adult↗

The treatment of hypogonadotrophic hypogonadism in men by the pulsatile infusion of luteinising hormone-releasing hormone.

The effects of chronic subcutaneous infusion of luteinising hormone-releasing hormone (LHRH) have been studied in a group of 17 male patients with hypogonadotrophic hypogonadism (HH). Ten of the patients had primary and seven secondary failure of gonadotrophin release, and all but four had previously been treated with gonadotrophin injections. Treatment was continued for between one and 18 months and was well tolerated by all except one patient who became allergic to LHRH. An increase in the basal gonadotrophin concentrations occurred in all except four patients within one week of the initiation of therapy, and this was associated with a rise in the serum testosterone level in eight patients. Increased spermatogenesis was demonstrated in seven cases and three pregnancies have resulted thus far. Pituitary desensitisation to the effects of LHRH was found in five subjects with primary HH who failed to produce any increase in testosterone secretion despite an initial stimulation of gonadotrophin release. We conclude that chronic pulsatile infusion of LHRH is an effective technique for the treatment of some cases of hypogonadotrophic hypogonadism.

Adult↗

The action of low- and high-chlorinated biphenyl mixture on prepubertal porcine ovary: steroid secretion and cells apoptosis.

OBJECTIVE: To compare the effects on ovarian function of low chlorinated polychlorinated biphenyls (PCBs) mixture generally distributed at a faster rate and metabolised to a greater extent (Delor 103) with high chlorinated PCBs mixture which are accumulated in large amounts in biological samples (Delor 106). METHODS: Theca interna and granulosa cells were isolated from prepubertal porcine follicles and initially cultured in M199/CS without test compounds for 24 hrs to allow for cell attachment to the wells. After 24 h, the medium was discarded and 0.3 ml of fresh M199 alone was added to the control culture, while Delor 103 or Delor 106 at concentrations of 0.02, 0.2 or 2 ng/ml medium were added to the cultures. For analysis of steroid levels, the media were collected after 24 hrs (single exposure) or 72 hrs (repeated exposure) and frozen at--20 degrees C. Additionally, after 72 hrs, LDL test was used to show the action of both mixtures on the cell viability and cells were used for the measurement of caspase-3 activity. RESULTS: An increase in testosterone secretion after the single exposure and strong stimulatory action on estradiol secretion was noted after permanent treatment with Delor 103. In Delor 106 treated cultures, antiestrogenic action after the single exposure and strong estrogenic action in permanently treated cells was observed. Both mixtures had no effect on cell viability and apoptosis. CONCLUSIONS: By stimulation of estradiol secretion from ovarian follicles in prepubertal animals, PCB mixture could be responsible for premature development of follicles and in consequence, premature sexual maturation.

Analysis of Variance↗

Effect of naloxone on the plasma levels of LH, FSH, prolactin and testosterone in Beetal bucks.

Ten adult male Beetal goats were used for the study to elucidate the modulation of gonadotrophin, prolactin and testosterone secretion by endogenous opioid peptides. An indwelling catheter was placed in the jugular vein of each buck 20h before the onset of the experiment. Bucks were divided randomly into two groups: Group I (n=5) received naloxone at a dose rate of 1mg/kg body weight (BW) and Group II (n=5) received naloxone at a dose rate of 2mg/kg BW intravenous. Blood samplings were done from 2h before treatment until 2h after treatment at 15min intervals. Blood samples were quantified for plasma LH, FSH and prolactin concentration using a heterologous double antibody radioimmunoassay (RIA) and testosterone concentration was quantified by coat-a-count RIA kit. The mean plasma LH levels during pretreatment phase were 0.41+/-0.03ng/ml in Group I and 0.44+/-0.02ng/ml in Group II which significantly (p<0.05) increased to 0.91+/-0.05ng/ml in Group I and 1.53+/-0.07ng/ml in Group II. The mean plasma FSH levels did not show a difference in pre- and post-treatment animals in both groups. A significant (p<0.05) increase in plasma testosterone concentration was observed in both groups after naloxone treatment, whereas, a decrease (p<0.05) was observed in plasma prolactin levels after naloxone treatment. Thus, it can be concluded that endogenous opioids do play an important role in modulating plasma LH, prolactin and testosterone concentrations in male goats.

Journal Article↗

Changes in testicular blood flow and testosterone production during aspermatogenesis after irradiation.

Exposure of the testes of anaesthetized adult rats to 527 rads of gamma-irradiation caused testis weight to fall slowly at first and then more rapidly from 21 days afterwards, reaching a minimum at 52 days, when spermatogenesis was severely disrupted. The weights of the accessory organs and the concentrations of testosterone in peripheral blood were slightly reduced; the concentrations in blood from the testicular veins were lower than control at shorter intervals after irradiation, but at later times tended to be similar or greater than control. Testicular blood flow per testis followed testis weight closely, and as a result the production of testosterone by the smaller testes (calculated as the product of plasma flow and the veno-arterial difference in testosterone concentration) was markedly reduced especially when the rats had been stimulated with human chorionic gonadotrophin (hCG). Serum FSH and LH rose appreciably as testis weight fell but there was a proportionately greater rise in FSH than LH, in comparison with surgically castrated animals. Increased amounts of extratubular, extracellular fluid were found in the aspermatogenic testes, but injection of hCG still caused increases in capillary permeability and the amount of fluid in the testis. These results indicate that during aspermatogenesis following irradiation (as with heat and efferent duct ligation) the capacity of the testes to secrete testosterone is severely limited by decreased testicular blood flow, not by the ability of the Leydig cells to release testosterone into their immediate environment.

Animals↗

The effects of continuous treatment of stallions with high levels of a potent GnRH analogue.

The effect of long-term treatment of stallions with a powerful gonadotrophin-releasing hormone (GnRH) analogue was investigated. In the first part of the study, 9 sexually mature pony stallions were allocated to 1 of 3 groups, each of which was treated with 240 micrograms or 60 micrograms Buserelin per day administered by subcutaneously sited osmotic pumps or 30-50 micrograms Buserelin per day via solid, slow-release implants injected subcutaneously. Peripheral blood plasma and serum samples were collected frequently and assayed for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and testosterone. No significant differences were seen between either high of low dose rates: in all treatment groups, serum and plasma concentrations of FSH, LH and testosterone rose sharply following insertion of pumps ofr implant. The levels remained elevated for 3-10 days in most animals, after which they returned to pre-treatment of lower values. In a second experiment, single implants, formulated to deliver 120 micrograms Buserelin per day for 28 days, were injected subcutaneously in to 2 pony stallions on 4 occasions at 5-day intervals. Gonadotrophin and testosterone secretions were temporarily stimulated in response to the first implant, but thereafter returned to pre-treatment or lower levels and showed no further stimulation following injection of subsequent implants. In a third experiment designed to establish the effects on libido and spermatogenesis of chronic treatment with levels of Buserelin (shown previously to depress gonadotrophin concentrations in stallions), 3 fertile pony stallions received subcutaneous implants at 2- to 5-week intervals for 12 months. Three untreated pony stallions acted as controls. Weekly blood samples were collected from both groups to monitor levels of FSH, LH, testosterone and oestrone sulphate. Semen was collected daily for 6-10 days both before treatment and at 3-month intervals thereafter in order to establish daily sperm output (DSO) and assess libido. Gonadotrophin, testosterone and oestrone sulphate levels were all lower in the treated group compared with either pre-treatment or control values. DSO was reduced by at least 50% throughout the treatment period in treated stallions but 7 months after insertion of the last implant it had returned to pre-treatment values. No significant effects on other semen characteristics were noted and there were no noticeable changes in libido of treated animals throughout the period of the experiment.

Animals↗

[The castration of male lambs by immunization against GnRH].

The objective of this study was to evaluate the effect of a GnRH-vaccine in the ram lamb. Experiments were performed using 20 male lambs, randomly divided into a test (GnRH-immunization) and control group (physiological NaCl-solution). At a body weight of 20 kg (age 2-3 months) and three weeks later, all animals of the test group received 2 ml of Improvac (CSL Limited, Parkville, Victoria, Australia). The body weight as well as the blood testosterone concentration were measured weekly for 16 weeks. Thereafter, blood samples for testosterone analysis were taken monthly in immunized lams only. After the booster injection testicular growth was suppressed and plasma testosterone remained at low values < 0.1 ng/ml for at least 12 weeks. The mean corresponding testosterone concentrations for the control lambs ranged between 0.1 and 0.9 ng/ml plasma. An increase of testosterone was observed in 8 of 10 immunized animals between 3 to 7 months after the booster dose. The control lambs showed a tendency for better growth rate than vaccinated animals, but the difference was not significant. Our results demonstrate that in prepubertal ram lambs two immunizations with Improvac, three weeks apart, can suppress testosterone secretion and testicular growth at least for three months after the booster injection. For a suppression of reproductive function longer than three months after the second vaccination, a third immunization is needed at this time or when testicular growth is beginning.

Animals↗

The increase in testicular vascular permeability induced by human chorionic gonadotrophin involves 5-hydroxytryptamine and possibly oestrogens, but not testosterone, prostaglandins, histamine or bradykinin.

Possible intermediates in the response of the rat testicular vasculature to human chorionic gonadotrophin (hCG) have been investigated. Ketanserin, an antagonist of 5-hydroxytryptamine, significantly reduced the increase in 1-h albumin space seen 20 h after hCG, as did one aromatase inhibitor (1,4,6-androstatriene-3,17-dione), but the effect of another (testolactone) did not reach significance. Aminoglutethimide, which inhibits overall steroid synthesis as well as aromatase, reduced the albumin space in both control and hCG-injected rats but the hCG response, as judged by the ratio between treated and control rats, was unaffected. Inhibitors of overall steroid synthesis (WIN 32,729), prostaglandin synthesis (meclofenamic acid or indomethacin) and angiotensin converting enzyme (captopril) and blockers of H1 and H2 histamine receptors (mepyramine, cimetidine or ranitidine) were without effect. The time course of the vascular response to hCG is quite different from the response in testosterone secretion by the testis. Considerable numbers of mast cells were found in the vicinity of the testicular artery in the testicular capsule, and these may be a source of 5-hydroxytryptamine.

Aminoglutethimide↗

Effects of a gonadotropin-releasing hormone agonist implant on reproduction in a male marsupial, Macropus eugenii.

This study evaluated the potential of slow-release GnRH agonist (deslorelin) implants to inhibit reproductive function in the male tammar wallaby. The specific aim was to measure the effects of graded dosages of deslorelin on testes size and plasma LH and testosterone concentrations. Adult male tammar wallabies were assigned to four groups (n = 6 per group) and received the following treatment: control, placebo implant; low dose, 5 mg deslorelin; medium dose, 10 mg; high dose, 20 mg. All dosages of deslorelin induced acute increases (P < 0.001) in plasma LH and testosterone concentrations within 2 h, with concentrations remaining elevated during the first 24 h but returning to pretreatment levels by Day 7. Thereafter, there was no evidence of a treatment-induced decline in plasma testosterone concentrations. There was no detectable difference in basal LH concentrations between treated and control animals, nor was there a significant change in testes width or length (P > 0.05). These results suggest that the male tammar wallaby is resistant to the contraceptive effects of chronic GnRH agonist treatment. Despite the maintenance of testosterone secretion, the majority of male tammars (10 of 17) failed to respond to a GnRH challenge with a release of LH between Days 186 and 197 of treatment. The failure of animals to respond to exogenous GnRH suggests a direct effect of deslorelin on the pituitary, resulting in a level of desensitization that was sufficient to inhibit a LH surge but insufficient to inhibit basal LH secretion. The variation between animals is believed to result from earlier recovery of some individuals, in particular those that received a lower dose, or individual resistance to the desensitization process.

Animals↗