4-Tert-octylphenol (OP) is a prevalent environmental pollutant that has been shown to exert both toxic and estrogenic effects on mammalian cells. The effects of OP on the reproductive system of adult male vertebrates are virtually unknown. In the present study, we investigated the effects of chronic exposure to OP on reproductive hormone secretion in the adult male rat and compared the results qualitatively with those observed in other male rats treated chronically with estrogen. We injected corn oil vehicle or OP (20 or 80 mg) or estradiol valerate (EV; 0.8 or 8 microg) in oil s.c. into 2-mo-old male rats thrice weekly for either 1 or 2 mo. The 80-mg dosage of OP and one or both dosages of EV had the following effects: decreased anterior pituitary gland (APG) and serum LH and FSH concentrations; increased APG and serum prolactin (PRL) concentrations; increased APG/body weight ratios; decreased serum testosterone concentrations; decreased hematocrit; and decreased food consumption and body weight gain. To evaluate the response of the hypothalamus-APG to gonadal removal, we orchidectomized some of the rats after the end of treatment and decapitated them 3 wk later. In orchidectomized controls, serum LH and FSH concentrations rose markedly and serum PRL concentrations decreased. Similar changes were seen in orchidectomized rats treated previously with 20 or 80 mg OP. Moreover, there were no differences in mean serum LH, FSH, or PRL concentrations between controls and rats treated previously with either dosage of OP at 3 wk after orchidectomy. The results demonstrate that chronic administration of OP to adult male rats can adversely affect the secretion of reproductive hormones and strongly suggest that OP exerts these effects by acting like an estrogen. The opposite changes in LH, FSH, and PRL secretion observed after cessation of treatment with OP and orchidectomy suggest that chronic treatment with OP under the conditions of the present study did not result in any significant permanent deleterious effects on gonadotrophs or lactotrophs or the hypothalamic neurons controlling the secretion of the gonadotropins or PRL.

Chronic administration of the environmental pollutant 4-tert-octylphenol to adult male rats interferes with the secretion of luteinizing hormone, follicle-stimulating hormone, prolactin, and testosterone.

To ascertain whether changes in the pattern of GnRH release from the hypothalmus occur during the 4-day rat estrous cycle, the pattern of LH release was characterized on each day of the estrous cycle, and the results were interpreted in light of the changes in pituitary responsiveness to GnRH previously described by this laboratory to occur during this time. Blood samples were taken from intact, freely moving rats via venous catheters at 6- to 10-min intervals for 3-4 h. LH pulse height and LH interpulse interval were quantified on each day of the cycle, and the transition on the afternoon of proestrus from tonic LH release to the preovulatory LH surge was detailed. The effects on the pattern of LH release during estrus of small doses of GnRH (0.4 ng) and the continuous infusion of the opioid antagonist naloxone were also examined. Plasma LH concentrations (NIAMDD rat LH-RP-1) were determined with a highly sensitive LH RIA. LH pulses were identified using the PULSAR algorithim. The LH interpulse intervals of 46 +/- 2 min on diestrous-1 day, 49 +/- 4 min on diestrous day 2, and 60 +/- 8 min on proestrus immediately before the LH surge were not significantly different. There were no changes immediately preceding the preovulatory LH surge on the afternoon of proestrus in either the LH interpulse interval or the LH pulse height. Instead, the transition from tonic LH secretion to the preovulatory LH surge was found to occur abruptly. These data suggest that an abrupt increase in GnRH secretion during the afternoon of proestrus initiates the dramatic rise in LH concentrations. The pattern of LH secretion during the day of estrus differed significantly from that on the other days of the cycle in that no LH pulses were observed. However, the administration of small pulses of GnRH elicited physiological elevations in LH release. Furthermore, the continuous infusion of naloxone to estrous rats immediately stimulated a pulsatile pattern of LH secretion, with a LH interpulse of 56 +/- 4 min. These data indicate that the absence of LH pulses during estrus may result from a deficit in GnRH release. Similar modifications in GnRH release during the other days of the cycle were inferred from the observed changes in LH pulse heights. The LH pulse height of 21 +/- 3 ng/ml on diestrous day 2 was significantly less than the LH pulse height of 41 +/- 4 ng/ml on diestrous day 1 or 35 +/- 4 ng/ml on proestrus before the surge.(ABSTRACT TRUNCATED AT 400 WORDS)

Changes in the Pulsatile Pattern of Luteinizing Hormone Secretion during the Rat Estrous Cycle

Effect of ovarian hormones on conflict behavior

Gonadotropin-releasing hormone immunoreactive neurons with access to fenestrated capillaries in mouse brain.

The inhibition of LH secretion during lactation may be the consequence of a pituitary insensitivity to GnRH stimulation and/or an inhibition of GnRH release from the hypothalamus. To assess the contribution that these mechanisms may make to the suppression of LH secretion during lactation, we described the pattern of LH secretion in lactating rats and the magnitude of LH secretion in response to a GnRH stimulus. We assessed the effect of the strength of the suckling stimulus (two and eight pups), the length of lactation (5 and 10 days), and the presence of the ovaries on the pattern of LH secretion. We also examined the pattern of LH secretion after removal of a large suckling stimulus. In the intact rat, the pattern of LH secretion during lactation was uniformly nonpulsatile, despite significant differences between animals suckling two and eight pups in pituitary responsiveness to GnRH. In intact rats suckling two pups during day 10 of lactation, significant LH secretion was stimulated by 0.4-ng pulses o...

The suppression of pulsatile luteinizing hormone secretion during lactation in the rat.

Experiments weie conducted to determine the effects of neonatal administration of L-monosodium glutamate (MSG) on behavioral and endocrine function in the female rat. Administration of MSG (4 mg/kg bo

Monosodium Glutamate Disruption of Behavioral and Endocrine Function in the Female Rat

Experiments were conducted in vivo to investigate further if the control of the pulsatile plasma LH phenomenon in ovariectomized (OVX) rats is located in the brain or in the adenohypophysis. Luteinizing hormone releasing hormone (LHRH) was infused at a constant rate (2--100 ng/h) through an indwelling venous cannula in unanesthetized, unrestrained OVX rats. Blood samples were collected at 5-min intervals through a second venous cannula prior to and during LHRH infusion for subsequent radioimmunoassay of plasma LH. LHRH infusion at 12.5, 50 and 100 ng/h did not interfere with the magnitude or the periodicity of LH pulses in plasma but the range within which plasma LH fluctuated was elevated. Phenobarbital (75 mg/kg BW; i.p.) blocked the pulsatile plasma LH and maintained the plasma LH nearly constant at reduced levels. Pulse i.v. injections of LHRH but not constant rate i.v. infusions restored pulsatile LH patterns in phenobarbital-treated OVX rats. The results are consistent with the view that pulsatile LHRH release is responsible for the pulsatile nature of plasma LH in OVX rats. The results do not support the concepts of a short-loop feedback of LH or an ultra-short-loop feedback of LHRH on LH secretion at least on an acute basis.

Plasma LH patterns after LHRH infusion in long-term, unanesthetized ovariectomized rats. Evidence for neural control of the pulsatile LH phenomenon.

We investigated the effects of hypothalamic arcuate nuclei destruction on the postovariectomy rise in plasma luteinizing hormone (LH) concentration and the pulsatile LH release mechanism in ovariectomized rats. Rats were injected with 1, 2, or 4 mg/g body wt of L-monosodium glutamate (MSG) on Days 1, 3, 5, 7, and 9 of life to lesion the arcuate nuclei. They were then ovariectomized as adults and used 2 or 4-8 weeks later. Serial blood sampling at 10-min intervals and measurement of plasma LH concentration revealed elevated plasma LH levels which fluctuated in a pulsatile fashion in all control and 1 and 2 mg/g/MSG-treated rats. In 4 mg/g MSG-treated rats, plasma LH levels were lower than in controls of both time periods after ovariectomy due to a decrease in the amplitude and/or frequency of LH pulses. Phenobarbital was administered to all 4- to 8-week ovariectomized rats to block endogenous pulsatile LH release. In phenobarbital-blocked rats, three sequential iv injections of LH releasing hormone (LHRH) caused substantial elevations in plasma LH concentrations even in the 4 mg/g MSG-treated animals which had low plasma LH concentrations during control bleedings prior to the injection of phenobarbital. The results indicate that the postovariectomy rise in plasma LH concentration and the associated pulsatile LH release mechanism are functional in rats with extensive arcuate nucleus lesions. The diminution in the rise in plasma LH levels and the decreased amplitude and/or frequency of LH pulses in the MSG-treated rats is likely due to a diminution in hypothalamic LHRH release.

Effects of hypothalamic arcuate nucleus lesions on pulsatile luteinizing hormone concentration in ovariectomized rats.

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R. Sridaran

Papers

Monosodium Glutamate Disruption of Behavioral and Endocrine Function in the Female Rat

Plasma LH patterns after LHRH infusion in long-term, unanesthetized ovariectomized rats. Evidence for neural control of the pulsatile LH phenomenon.

Effects of hypothalamic arcuate nucleus lesions on pulsatile luteinizing hormone concentration in ovariectomized rats.

Ovarian Involvement in the Timing Mechanism that Controls Ovulation in Rats