Correlation of age-associated increases in follicle stimulating hormone secretion with decreases in antral follicles: failure of progesterone-induced acyclicity to prevent these changes.

It is well known that the number of follicles in the mammalian ovary decreases with age. In light of previous data from this laboratory showing age-related alterations in the secretion and production of follicle-stimulating hormone (FSH) in rats by 5-6 months of age, one objective of the present study was to determine if alterations in FSH secretion were accompanied by changes in the number of antral follicles. A second objective of this study was to determine whether or not interruption of cyclic activity by continuous progesterone (P) treatment could decelerate age-associated changes in FSH secretion possibly by retarding the depletion of follicles through ovulation. For this study, one group of 4-day cycling, 7-week-old rats received one empty Silastic implant while another group received 3-40 mm implants containing 30 mm crystalline P. Implants were replaced every 2 weeks until the animals were 5 months old. Progesterone-implanted rats were acyclic during treatment exhibiting predominantly leukocytic vaginal smears. Regular 4-day cycles resumed when P implants were withdrawn (rats approximately 5-6-months-old). A group of 2-3-month-old untreated rats were used for comparison. As expected from our previous results, serum FSH levels at 1600 h on estrus were significantly higher in 5-6-month-old rats receiving empty capsules than in younger rats. Serum FSH concentrations measured in P-treated rats at this time also were significantly higher than levels of this gonadotropin measured in younger rats. Ovaries of older control and P-treated rats contained significantly fewer medium and large antral follicles (greater than 250 microns) than the ovaries of younger rats despite the curtailment of estrous cyclicity and ovulation by continuous P treatment. Interestingly, P treatment prevented the age-associated decrease in thymus weight. Taken together, the present observations suggest that a decrease in the number of growing follicles may be a factor contributing to early age-related alterations in FSH secretion. Furthermore, the prevention (at least temporarily) of age-related thymic involution by P treatment may be indicative of an interrelationship between thymic and reproductive aging.

Acute delta 9-tetrahydrocannabinol exposure: effects on hypothalamic-pituitary-testicular activity in mice.

The endocrine functions of the median eminence, pituitary and testes were examined in male mice after exposure to delta 9-tetrahydrocannabinol (THC) either in vivo or in vitro. The secretion of luteinizing hormone-releasing hormone (LHRH) under basal conditions, and in the presence of norepinephrine (NE; 60 microM), was significantly enhanced in median eminence fragments obtained 1 hr post-treatment with THC (50 mg/kg), while addition of THC (250 ng/ml) to the incubation media enhanced clonidine, as well as NE-stimulated LHRH release, but did not affect basal LHRH release. In vitro exposure to THC also enhanced LHRH-stimulated LH release by pituitaries, but did not affect basal secretion rates. In vivo THC exposure tended to enhance pituitary responsiveness to LHRH, although this effect was not statistically significant. In testicular perifusions, addition of THC at a concentration of 250 ng/ml completely blocked hCG-stimulated T secretion within 30 min. The suppressive effects of a lower dose of THC, 25 ng/ml, required 60 min to inhibit T production, an effect which persisted for 60-80 min post-THC. These findings indicate that THC exposure enhances responsivity at neuroendocrine target sites, but attenuates gonadotropin-stimulated testicular steroidogenesis.

Differential regulation of pulsatile luteinizing hormone (LH) and follicle-stimulating hormone secretion in ovariectomized rats disclosed by treatment with a LH-releasing hormone antagonist and phenobarbital.

Although pulsatile LH release in ovariectomized (OVX) rats appears to be controlled by pulsatile discharges of LHRH, the neuroendocrine regulation of episodic FSH release remains to be explored. The main objective of the present study is to compare and contrast the effects of a potent LHRH antagonist (ALHRH) and a central nervous system depressant, phenobarbital (PhB), on pulsatile LH and FSH release in OVX rats. Three to 4 weeks after ovariectomy, blood samples were obtained at 10-min intervals for 3 h, after which LHRH was injected and sampling continued for an additional hour. In control OVX rats, periodic increases in plasma LH and FSH levels occurred approximately every 30 to 60 min, respectively. Treatment of OVX rats with PhB several hours earlier resulted in a suppression of mean plasma levels and pulse frequencies of both LH and FSH. Interestingly, PhB suppressed the pulse amplitude of LH, but not of FSH. Phenobarbital increased pituitary LH responses to LHRH, but did not alter the FSH responses. When ALHRH was given to OVX rats 24 h before blood sampling, mean plasma LH levels as well as LH pulse frequency and amplitude were severely diminished. In striking contrast, ALHRH did not affect the frequency or amplitude of FSH pulses. However, mean plasma FSH levels were suppressed to 31% of levels measured in control OVX rats. These results demonstrate that in contrast to LH secretion, FSH secretion in OVX rats appears to be regulated by two distinct neuroendocrine mechanisms: an LHRH-dependent mechanism controlling the nonepisodic component of FSH secretion (baseline secretion) and a LHRH-independent mechanism controlling pulsatile FSH release.

Dose-dependent inhibition of the preovulatory surges of gonadotropins and prolactin by the antiestrogen CI-628: possible sites of action.

The present series of experiments was conducted in an attempt to correlate previously reported dose-dependent and site-selective inhibitory effects of an antiestrogen, CI-628, on 17 beta-estradiol (E2)-receptor interactions in the anterior pituitary gland (AP) and hypothalamus with its effects on the preovulatory surges of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin. The effects of CI-628 on the response of the AP to luteinizing hormone-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) also were examined. In the first study, rats exhibiting 4-day estrous cycles were injected with various doses (0.02, 0.20, 2.0, and 20 mg/kg) of CI-628 or vehicle at 0900 h on diestrus-2 and proestrus. The preovulatory LH surge and both preovulatory and secondary FSH surges were marginally affected by 0.02 mg/kg CI-628, but were completely abolished by higher doses. In contrast, a dose of 0.20 mg/kg only delayed the prolactin surge; however, higher doses were effective in extinguishing cyclic prolactin release. In a second experiment, CI-628 in rats treated on diestrus-2 and proestrus exerted a dose-dependent suppression of the AP LH response to an initial injection of LHRH on proestrous afternoon in rats whose endogenous LH surges were blocked by phenobarbital. However, AP LH responses to a second LHRH injection to assess the self-priming capacity of LHRH were attenuated only in rats given 0.20, 2.0, and 20 mg/kg CI-628. Contrastingly, the AP prolactin response to TRH was suppressed only in rats given 0.20 mg/kg CI-628.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of advancing age on hypothalamic neurotransmitter content and on basal and norepinephrine-stimulated LHRH release.

In order to elucidate possible mechanism(s) responsible for the age-related decline in LH secretion, basal and norepinephrine (NE)-stimulated LHRH release was measured from median eminence (ME) fragments of 4-, 11-, 18- and 27-month-old male F344 rats. Serum LH levels declined significantly between 11 and 18 months and were still lower at 27 months of age, while testosterone levels declined continuously between 4 and 27 months. Hypothalamic NE and dopamine (DA) content also declined significantly with age, while serotonin and 5-hydroxy-indoleacetic acid content increased with age. Despite the decline in serum LH levels with age, in vitro basal LHRH release increased gradually with age as did NE-stimulated LHRH release. These data suggest that the age-related reduction in LH secretion by the male rat is due to a reduction in hypothalamic NE metabolism and not to an inability of the LHRH neuron to respond to NE stimulation.

Effect of suppression of the surge of follicle-stimulating hormone with porcine follicular fluid on follicular development in the rat.

To examine the manner in which the FSH surge of one oestrous cycle recruits follicles for ovulation in the subsequent cycle, porcine follicular fluid (PFF) was used to alter the pattern of endogenous FSH secretion during the periovulatory period. OVaries of animals killed at oestrus or metoestrus were examined histologically for the presence of large follicles (greater than 400 micrometers in diameter) after treatment. Large follicles were absent in ovaries of PFF-treated animals at oestrus, while control rats had an average of 2.7 large follicles per ovary. By metoestrus, however, ovaries of rats treated with PFF contained several large, healthy follicles. Only when PFF treatment was continued throughout the evening of oestrus was the appearance of large follicles prevented at metoestrus. Our results suggest that the prolonged oestrus portion of the FSH surge, rather than the pro-oestrous portion, is responsible for follicular recruitment during the normal oestrous cycle in the rat. They also indicate that compensatory follicular development occurs in response to the FSH rebound which has been shown to follow FSH suppression.

Organic anions induce colinic secretion.

Experiments were conducted by instilling test solutions into the cleaned colon of anesthetized rats. Isotonic test solutions at an acid (2.9% or neutral (7.0) pH and containing acetic acid or acetate ions were used. At the lower pH, acetic acid was absorbed well absorbed and the colon absorbed fluid. The secretory effect could not be reproduced by hydrochloric acid solutions at pH 2.9. Fluid secretion induced by acetic acid was associated with discharge of mucus from goblet cells. The interference of colonic absorption by acetic acid might be important in some diarrheal diseases.