Georgia L. Rehnberg

Effect of lindane on hormonal control of reproductive function in the female rat.

The effect of the gamma isomer of 1,2,3,4,5,6-hexachlorocyclohexane, lindane, on reproductive function in the female rat was examined in two experiments. In the first experiment, chronic treatment with 0, 5, 10, 20, and 40 mg/kg lindane delayed vaginal opening and disrupted ovarian cyclicity until approximately 110 days of age. Thereafter, regular ovarian cycles were present in the majority of females in all dose groups. When killed on the day of vaginal proestrus, the females receiving the two higher doses of lindane had smaller pituitary and uterine weights, lower serum and pituitary luteinizing hormone (LH) and prolactin, and higher pituitary follicle stimulating hormone (FSH) concentrations than the oil-treated control females. Serum estrogen concentrations were not different from controls in the 5 and 20 mg/kg groups, significantly greater than the controls in the 10 mg/kg group, and significantly less than the controls in the group receiving 40 mg/kg. In a second experiment, the uterine weight and pituitary hormone response of 28-day-old, lindane-treated females to a 10-micrograms injection of estradiol benzoate (EB) were investigated. The uteri of the lindane-treated prepubertal females were smaller than controls at 30 hr after EB injection. Furthermore, the EB-induced increase in serum luteinizing hormone, observed at 30 hr after EB injection, was lower in the lindane-treated animals. Similarly, the reduction in pituitary LH, FSH, and prolactin induced by EB was not as great in the lindane-treated animals as in the controls. Serum estrogen concentrations in the lindane-treated animals were not different from controls. These data indicate that lindane may effectively block the response of estrogen-dependent tissues to this ovarian steroid hormone and that this apparent antiestrogenic effect of lindane is responsible for the disturbances observed in the neuroendocrine control of ovarian function in the rat.

Serum and testicular testosterone and androgen binding protein profiles following subchronic treatment with carbendazim

While the general toxicity of the benzimidazole pesticides for mammals is low, one of these compounds, carbendazim (MBC), causes degeneration of testicular tissue and decreases spermatogenic activity at doses well below the LD50 value. A study conducted by S. D. Carter, R. A. Hess, and J. W. Laskey (1987, Biol. Reprod. 37, 709-717) showed that treatment with 400 mg/kg/day MBC resulted in severe seminiferous tubular atrophy and infertility. Since spermatogenesis is an androgen-dependent process, we characterized the effects of MBC (0-400 mg/kg/day) on the endocrine function of the rat testes. Following subchronic (85 day) exposure, serum hormones (TSH, LH, FSH, and Prl) were measured as were androgen binding protein (ABP) and testosterone in testicular fluids (interstitial fluid and seminiferous tubule fluid). In addition, the functional capacity of the Leydig cell to secrete testosterone was assessed in vitro following an hCG challenge. Subchronic treatment with MBC at doses of 50-100 mg/kg/day had no effect on pituitary or testicular hormone concentrations: 200 mg/kg/day elevated the testosterone concentration in the seminiferous tubule fluid and the ABP concentration in both the interstitial fluid and the seminiferous tubule fluid without affecting serum testosterone or ABP concentrations. The 400 mg/kg/day dose resulted in increased concentration of both testosterone and ABP in the interstitial fluid and seminiferous tubule fluid and elevated serum ABP, with no change in serum testosterone. This endocrine profile is consistent with the testicular atrophy and Sertoli cell-only syndrome seen in these animals as reported by Gray et al. (1987, Toxicologist 7, 717). We conclude that seminiferous tubule fluid testosterone may be a result of two factors: (1) increased interstitial fluid testosterone concentrations and (2) decreased testosterone outflow from the testis to the general circulation. Also, increased ABP in the interstitial fluid may reflect a change in the relative secretion of ABP into the interstitial fluid and the seminiferous tubules.

Effects of the benomyl metabolite, carbendazim, on the hypothalamic-pituitary reproductive axis in the male rat.

Carbendazim (MBC), the bioactive metabolite of the fungicide benomyl, has been reported to induce a number of testicular alterations in male rats. Since it is possible that extragonadal changes contribute to the appearance of such effects, the present study focused on the presence of concurrent endocrine changes in the hypothalamic and pituitary components of the brain-pituitary-testicular axis. Subchronic administration of MBC (50, 100, 200 or 400 mg/kg) was found to cause a dose-related elevation in serum follicle stimulating hormone (FSH) and pituitary luteinizing hormone (LH). Values for prolactin and thyroid-stimulating hormone remained unchanged. No statistical differences in gonadotropin-releasing hormone concentrations were present in mediobasal hypothalamus, although an elevation in anterior hypothalamic values was found at the low dose, followed by a dose-related decline. These findings demonstrate that previously reported gonadal differences following subchronic exposure to carbendazim are accompanied by alterations elsewhere in the reproductive system which appear to involve both changes in Sertoli cell-pituitary feedback signals and direct effects of the compound on the central nervous system.

Neuroendocrine control of reproductive function in the aging female rodent.

T he age-related decline in reproductive capacity in mammals provides a unique opportunity to study aging within a complex neuroendocrine system. In the female, reproductive aging is a consequence of a progressive series of changes initiated during early development and continuing through adulthood. Significantly, the course of these events is not immutable, as their progression can be advanced or delayed in time with appropriate manipulation. Our knowledge of the interrelationships that exist within this neuroendocrine system and the ways in which they change over time is important not only to a full understanding of reproductive aging, but also to a better comprehension of the aging process in general. Research on reproductive aging in the female rodent traditionally derives from two interrelated areas of interest. The first stems from clinical concerns about the deterioration of human reproductive capacity and the medical information that can be obtained by studying the decline in other mammalian species. The second involves the fundamental issue of aging per se and the unique characteristics of the reproductive

Effect of inhaled methanol on pituitary and testicular hormones in chamber acclimated and non-acclimated rats

Two experiments were conducted in which the acute effects of inhaled methanol on serum hormones associated with reproductive function in the male rat were evaluated. In the first experiment, rats exposed to methanol (0, 200, 5000 and 10,000 ppm) for 6 h were killed at the end of the exposure period (6 h) or the following morning (24 h). Also, because the process of exposure itself could modify neuroendocrine function, the effect of the handling associated with placing the rat in the exposure chamber was evaluated further by dividing the exposed animals into acclimated (2 weeks of prior handling) and non-acclimated groups. At 6 h, an effect of prior handling was noted in the sham-exposed rats, with serum luteinizing hormone (LH) of the non-acclimated group being greater than that of the acclimated group. Serum LH concentrations were altered by methanol exposure, but the direction of change and the exposure level at which an effect was noted differed between the acclimated and non-acclimated rats. Methanol (5000 ppm) reduced serum LH in the non-acclimated animals, while 10,000 ppm increased LH in the acclimated rats. Follicle stimulating hormone (FSH) and testosterone were unchanged by methanol in rats killed at 6 h. Thus, this experiment did not confirm earlier reports that exposure to 200 ppm for 6 h reduced serum testosterone. At 24 h, an effect of prior handling was still present in the hormonal measures, with serum and interstitial fluid testosterone concentrations being greater in the non-acclimated rats. Also, there was a dose x handling interaction with methanol exposure inducing an increase in serum testosterone in the non-acclimated rats (up to 5000 ppm) and a decrease in the acclimated rats (up to 10,000 ppm). In the second experiment, groups of acclimated and non-acclimated rats were exposed to 0 or 5000 ppm methanol for 1, 2 and 6 h and killed immediately after removal from the chamber. Serum LH, testosterone and FSH values were not different in sham- vs methanol-exposed rats at any time point. As in experiment 1, an effect of prior handling was noted. In general, the concentrations of these hormones and serum prolactin in the non-acclimated rats were greater than those observed for acclimated rats. Methanol exposure resulted in increased prolactin concentrations under both handling conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Age-related alterations in the stimulated release in vitro of catecholamines and luteinizing hormone-releasing hormone from the male rat hypothalamus

Using an in vitro perifusion system, the present study investigated the possibility that alterations in catecholamine and luteinizing hormone-releasing hormone (LHRH) secretion from the male rat mediobasal hypothalamus are present during the period of middle-age. The results indicate that, while tissue concentrations and baseline secretion of norepinephrine, dopamine and LHRH were similar between age groups, the patterns of dopamine and LHRH release in response to a series of depolarizing stimuli was different in the older animals. After all challenges, dopamine concentrations in the perifusate declined much more sharply for the middle-aged group, a finding that may be associated with a decrease with age in the pool of transmitter available for ready release. Also, tissue fragments from young adult rats were able to maintain the release of LHRH to a greater extent than tissue from the middle-aged animals, but only for the initial challenge period. The typical episodic pattern of LHRH release appeared to be disrupted in the older group following a second stimulus. It is possible that these age-related changes are early components of a dysruption in the hypothalamic mechanisms governing gonadotropin secretion.

Age-related changes in the regional distribution of hormones in the male rat anterior pituitary.

Some heterogeneity in the localization of hormone-containing cells has been reported in the mammalian anterior pituitary. Since age-related changes are present in pituitary hormone concentrations, the present study was designed to explore if such changes in the male rat are regionally consistent. The results show clear geographic patterns in the presence of immunoreactive LH, FSH, prolactin and TSH. In the two year-old male, specific regional declines in hormone concentrations were present. With one regional exception, such was not the case when values were expressed in total hormonal content. A fall in gonadotropins still appeared in the medial area of the most caudal strip. The results suggest that with age, there is a displacement of hormone-containing cells in the pituitary and that for the gonadotropes this effect appears to be more prominent within the medio-caudal area.