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Circulating plasma concentrations of LH from young mature (3-4 months old), middle-aged (15-18 months old) and aged (31-32 months old) male C57BL/6 mice, Syrian hamsters (3-4, 19-20 and 24-25 months old), Fischer 344 rats (3-4, 18-19 and 28-29 months old), Chinese hamsters (3-4, 19-20 and 29-30 months old) and Mongolian gerbils (3-4 and 19-22 months old) were analysed using a radioimmunoassay (RIA) and a radioreceptor assay (RRA). Male rats exhibited the greatest changes with advancing age: the oldest rats had an almost undetectable quantity of plasma LH, as measured by both assays. In contrast, the oldest male Syrian hamsters had significantly higher levels of LH than did younger animals. A significant decrease occurred in the amounts of LH detectable by RRA in middle-aged Chinese hamsters which was not evident with the RIA. There were no statistically significant differences in LH levels of C57BL/6 mice and gerbils with increasing age. The mean RRA:RIA ratios indicated that age-related differences in LH concentrations resulted from physiological changes in the secretion or the metabolic clearance of LH and not from changes in the biological potency of LH.

The autoregulation of testicular LH receptors was studied in Wx/Wv mice with germ cell aplasia and in normal (+/+) mice. To assess the effects of each individual allele, Wx/+ and Wv/+ mice were also examined. Basal testicular LH receptor concentration was higher in Wx/Wv mice than in all other genotypes, and higher in Wx/+ than in +/+ mice. Twenty-four h after injection of 0.3 IU hCG/g bw, LH receptor concentration was decreased in +/+ and Wv/+ mice, but not in Wx/Wv or Wx/+ animals. Administration of hCG caused a significant increase in plasma testosterone levels in all genotypes. However, injection of the highest dose of hCG used (0.9 IU/g bw) caused a significantly greater elevation in plasma testosterone in Wx/Wv than in +/+ mice. Plasma gonadotropin levels were significantly higher in Wx/Wv mice than in all other genotypes. The present results indicate that the Wx allele is responsible for the changes in testicular function observed in Wx/Wv mice, and suggest that this allele may be involved in the genetic regulation of testicular LH receptors in the mouse.

Effective balloon aortic valvuloplasty (BAV) is limited restenosis. After aortic valve restenosis six patients underwent repeat BAV. In spite of the use of larger balloons there was a trend toward a less satisfactory result after repeat BAV (0.98 +/- .26 cm2 vs. 1.2 +/- .26 cm2), which did not reach statistical significance, P = .14. Mortality of the patients at 6 months was 50%. Repeat BAV may be less efficacious than the original procedure.

The influence of different doses of bromocriptine (CB-154) on plasma levels of prolactin (Prl), FSH, LH and testosterone (T) in mature male rats and mice was studied. Daily subcutaneous administration of 360 micrograms of CB-154 in sesame oil was sufficient to induce maximal suppression of plasma Prl levels in mature male rats whilst subcutaneous implantation of two pellets of CB-154 and cholesterol, each containing approximately 6 mg CB-154, was effective in suppressing serum Prl levels in mature rats for at least four weeks. This was accompanied by a significant elevation of plasma levels of LH and FSH. A similar dose-response study in mature male mice suggested that relatively higher doses of CB-154 are required to suppress plasma levels of Prl in this species, although large doses of CB-154 can still increase plasma levels of gonadotrophins and T in male mice.

Castration produces hypertrophy of gonadotropes, stimulates a shift in storage patterns to cells that store LH and FSH together, and results in a significant rise in serum LH and FSH within 12 h. Adrenalectomy retards and attenuates this postcastration rise for 24 h (1, 2). In this study, we examined the effect of adrenalectomy on castration cell morphological development. The increased percentages of LH and FSH cells that are seen normally 24 h after castration were not seen if adrenalectomy or sham adrenalectomy was performed simultaneously. In fact, the percentages of LH cells were below control values. The expansion in the average area of LH and FSH cells was also retarded after simultaneous castration and adrenalectomy or sham adrenalectomy. The corticotrope population responded as expected to adrenalectomy and the surgical stress of castration, with an increase in the percentage and area of stained cells as well as partial degranulation. The serial sections showed no ACTH staining in gonadotropes after any of the surgical treatments. The gonadotropic storage patterns were altered, however. In castrated rats exposed to simultaneous adrenalectomy or sham adrenalectomy, the percentage of LH/FSH cells was reduced from 70% of gonadotropes in intact rats to 30%. Over 60% of the serially sectioned gonadotropes stored only one hormone, and these monohormonal cells tended to occur in clusters. Our experiments thus show that the gonadotropin storage pattern can be shifted with experimental manipulation. This may also reflect shifts in the site of hormone storage within a given cell. We suggest that adrenalectomy or sham adrenalectomy retards the postcastration rise in gonadotropins by preventing the immediate expansion of the granulated cell population and causing an apparent loss in the numbers of certain types of gonadotropes.

The regulation of testicular hCG binding and steroidogenesis in adult mutant mice with hereditary diabetes and obesity was studied. Low doses of hCG caused no change in hCG binding in obese (ob/ob) mice, whereas, in diabetic (db/db) mice, the increase in binding measured 24 h after hCG administration was not as great as in normal males. Intermediate doses of hCG caused a decrease in hCG binding in obese and normal mice, but not in diabetic animals. However, 72 h after injection of intermediate doses of hCG, a decrease in hCG binding also was observed in diabetic mice. Plasma testosterone was elevated 24 h after hCG injection in all types of mice studied, but the increase in diabetic mice was smaller than in normal animals. However, 72 h after treatment with hCG, plasma testosterone was still elevated in diabetic mice, but not in normal males. In vitro, hCG stimulated testicular testosterone synthesis in all groups of mice, but the observed increase was smaller in diabetic and obese than in normal animals. Plasma LH levels were higher in diabetic than in normal mice, whereas plasma FSH and prolactin levels were lower in obese mice than in normal animals. All parameters (i.e., LH receptors and circulating hormone levels) measured in yellow (Ay/a) mice were similar to those in normal (a/a) mice. The present study indicates that in these models for noninsulin-dependent diabetes, the testicular metabolism of LH receptors and capacity to secrete steroids is altered.

The reproductive capabilities of 6- and 24-month-old C57BL/6NNia male mice were compared after being paired for one month with a 4-month-old proven-fertile female. All of the younger males mated, with 96% yielding a litter; only 42% of aged males mated, with 65% siring young. There were no statistical differences in the litter sizes, nor any congenital defects noted in offspring from either age group. There was no evidence of aneuploidy in 10-day-old embryos sired from males of either age group. Aged males that failed to mate had lower body weight, a lower hematocrit, hypertrophied adrenal glands and seminal vesicles, decreased fructose levels in seminal vesicle fluid, atrophied testes with fewer sperm that were less motile, lower testosterone levels, and a greater percentage of degenerating epithelium lining seminiferous tubules. The latter group of aged mice, while appearing and acting as vigorous as aged mice that had mated, may have been experiencing disease processes associated with aging which subsequently impaired reproduction.

The effects of short-term and chronic lithium administration on the concentrations of plasma testosterone (T) and luteinizing hormone (LH) were evaluated in C57BL/6 mice, maintained on a fixed photoperiod of LD 14:10 (white lights on at 06:00 h, CST). Lithium chloride was injected intraperitoneally twice daily (at 09:00 and 16:00 h) in groups of adult male mice at a dosage of 2.5 meq/kg for 7 days, and 1.25 meg/kg for 21 days. Circulating levels of T and LH were measured by standard radioimmunoassay (RIA) methods. Plasma T levels showed a significant increase in mice treated with lithium for 7 days as compared to those in saline-injected control animals. However, there was no significant difference in the concentrations of plasma T between chronic (21 days) lithium-treated mice and the matched control. Plasma LH levels remained unchanged following both short-term and chronic lithium treatment.

Plasma levels of LH were measured in young sexually mature (2- to 5-month-old) and aged (13- to 20-month-old) female C57BL/6 mice, Syrian hamsters and Wistar rats using a radioimmunoassay (RIA) and a radioreceptor assay (RRA). There were no statistically significant differences when comparing data from the two assays when examining young oestrous and dioestrous mice. Aged oestrous and dioestrous mice exhibited significantly higher levels of LH as measured by RIA than by RRA. Levels of LH analysed by RIA were also higher in aged mice compared with those in younger mice. Comparing LH hamsters produced similar results. In contrasts, aged pseudopregnant rats exhibited significantly lower levels of plasma LH than younger dioestrous females and there were no differences in RIA and RRA values. There were also no differences when comparing data from the two assays in younger rats. The mean (+/- S.E.M.) RRA: RIA ratios of 0.96 +/- 0.05 (oestrous) and 0.96 +/- 0.04 (dioestrous) for younger mice and 0.92 +/- 0.08 for younger hamsters were significantly higher than the ratios of 0.66 +/- 0.05, 0.72 +/-0.05 and 0.71 +/- 0.05 respectively of their aged counterparts. The mean RRA: RIA ratios in the two age groups of rats were almost identical (0.79 +/- 0.05 and 0.80 +/- 0.10). These studies suggested that a portion of the higher LH levels detectable by RIA in some aged female rodents results from qualitative changes in the LH molecule.

Samples of plasma and pituitary homogenates collected from female Mongolian gerbils (3-4, 11-13 and 20-25 month-old) at various stages of the estrous cycle were analyzed by radioimmunoassay for luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (Prl). Plasma and pituitary LH concentrations were similar in all three age groups. Plasma FSH concentrations tended to increase with age while plasma Prl concentrations remained unchanged. Pituitary concentrations of FSH and Prl were variable between the age groups depending upon the stage of the estrous cycle. The inability of older gerbils to produce young appears to result primarily from age-related changes occurring in the uterus rather than from alterations in the hypothalamic-hypophyseal complex.

Introduction of the human growth hormone (hGH) gene fused with mouse metallothionein I promoter into domestic mice leads to ectopic synthesis of hGH, marked stimulation of somatic growth, and female sterility. Transgenic females (produced by mating transgenic males to normal females) mated but failed to become pregnant or pseudopregnant as evidenced by the recurrence of vaginal plugs every 5-7 days. Daily injections of 1 mg progesterone, starting on day 1 postcoitum (p.c.), maintained pregnancy, suggesting that the sterility of these animals is due to inadequate luteal function. In ovariectomized female transgenic mice, median eminence (ME) turnover of dopamine (DA) was increased, and plasma prolactin (PRL) levels were reduced, presumably because of the known lactogenic activity of hGH in rodents. From these observations we suspected that either 1) the corpora lutea of these animals are unresponsive to lactogenic hormones, or 2) hGH by stimulating tuberoinfundibular dopaminergic (TIDA) neurons interferes with the increase in PRL release that normally follows mating and this, in turn, leads to luteal failure. To distinguish between these possibilities, transgenic females were treated with PRL-secreting ectopic pituitary transplants from normal females of the same strain on day 1 p.c. Eight of ten treated females became pregnant and delivered litters. We conclude that infertility of transgenic female mice with hGH expression is due to activation of the TIDA system, suppression of endogenous PRL release, and luteal deficiency.