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Biomedical subjects

R W Steger

Publications and source records attributed to R W Steger.

At least 127 records · Page 7Linked to original sources

Aging and ovarian function in the white-footed mouse (Peromyscus leucopus) with specific reference to the development of preovulatory follicles.

A study was made of the effects of increasing age on uterine histology, follicular development and steroidogenesis within the ovary of the white-footed mouse (Peromyscus leucopus). The animals were autopsied on each day of the estrous cycle and ranged from 14 to 49 mos. of age. The data indicated that the animals maintained estrous cycles throughout their lifespan as judged by cyclic changes in uterine histology. In addition these studies showed that aging (1) did not alter ovarian concentrations of testosterone, 17 beta-estradiol or progesterone, (2) resulted in a decrease in the number of primary and preantral follicles during metestrus, proestrus and estrus, (3) increased the percentage of atretic preantral follicles during metestrus only, and (4) did not reduce the number of antral (preovulatory) follicles that develop by proestrus. These observations suggest that in P. leucopus the "rescue" of preantral follicles constitutes the mechanism which compensates for the decrease in the number of smaller follicles and allows the normal number of preovulatory follicles to develop and ovulate. It is also possible that this mechanism exists in the laboratory mouse and rat since species-specific numbers of preovulatory follicles develop in aged cycling animals despite an age-related decrease in the total follicular populations.

Aging↗

Effects of advancing age on the hypothalamic-pituitary-ovarian axis of the female white-footed mouse (Peromyscus leucopus).

Peromyscus leucopus, with an average lifespan of 48 months, showed unchanged levels of serum luteinizing hormone (LH), estradiol, progesterone, and pituitary LH and prolactin, between the ages of 12 and 48 months. Hypothalamic LH-releasing hormone (LHRH), norepinephrine and dopamine also remained unchanged with advancing age. Ovarian and uterine weight decreased with age, although the changes in uterine weight were not statistically significant. These data indicate that the hypothalamic-pituitary-ovarian axis remains intact with increasing age, accounting for the maintenance of fertility in these animals. The lack of significant changes in these parameters is in very marked contrast to those in the aging laboratory mouse and rat, which show derangements in their reproductive systems midway through their lifespans.

Aging↗

Effects of a prolactin-secreting pituitary tumor on hypothalamic, gonadotropic and testicular function in male rats.

The presence of a transplanted prolactin- and GH-secreting pituitary tumor (Furth MtT.215) in inbred male rats resulted in increased hypothalamic LHRH and pituitary LH content, decreased serum LH and testosterone concentrations, and very high serum prolactin values. The pituitary tumor also inhibited LH release by the in situ pituitary in response to orchidectomy, or orchidectomy, or adrenalectomy, and reduced the LH response to LHRH administration. Testes weight was significantly reduced and adrenal weight was significantly increased in the rats carrying pituitary tumors. These results that inhibitory effects of the transplanted pituitary tumor on LH and testosterone secretion were affected both a reduction in hypothalamic LHRH release and a reduced responsiveness of the pituitary to LHRH.

Adrenalectomy↗

Decreased pulsatile release of growth hormone in old male rats.

Pulsatile release of GH was compared in young (4-5 months old) and old (18-20 months old) male Sprague-Dawley rats using indwelling atrial cannulae. More than 57% of the young rats exhibited GH pulses greater than 300 ng/ml plasma, whereas only 7% of the old animals had GH pulses of similar amplitude. Trough GH values were not different between young and old rats, but during the 10.5-h sampling period, mean GH concentrations in young male rats were significantly greater than those in old male rats (175.3 +/- 20.9 vs. 70.2 +/- 7.6 ng/ml; P < 0.01). In another experiment, pituitary GH and hypothalamic somatostatin content were measured in young and old rats. The pituitary GH content was significantly greater in young than in old males (1187 +/- 95 vs. 670 +/- 93 microgram; P < 0.01). The immunoreactive somatostatin content in caudal areas of the hypothalamus was also greater in young than in old male rats (100.2 +/- 4.2 vs. 79.0 +/- 5.1 ng; P < 0.01). These observations demonstrate that GH secretion is depressed in old male rats, and this is associated with diminished pulsatile release of GH. The results also suggest that a relationship exists among the reduction in somatostatin content, pituitary GH content, and attenuated GH secretion in old male rats.

Aging↗

Relation of neuroendocrine system to the reproductive decline in aging rats and human subjects.

The relation of neuroendocrine functions to the reproductive decline was compared in human subjects and in rats of both sexes. The ovaries of rats remain potentially functional throughout the animal's life span, but cease to exhibit regular 4- or 5-day cyclic changes at about midelife. The loss of estrous cycles is believed to be due primarily to changes in hypothalamic neurotransmitters that lead to failure to exhibit cyclic surges in release of hypothalamic luteinizing hormone-releasing hormone and pituitary gonadotropins. Menstrual cycles normally cease in women between 40 and 50 years of age, primarily because the ovaries decline in their capacity to respond to gonadotropic stimulation with adequate production of estrogen and progesterone, and by ovulation, which in turn leads to increased gonadotropin secretion. In aging male rats, testosterone secretion by the testes decreases due to reduced stimulation by gonadotropins, in turn caused by decreased hypothalamic stimulation. Elderly men have been reported to show a reduction in testosterone and sperm production, accompanied by an increase in gonadotropin secretion, but more recent work in healthy, active men showed no increase in testosterone secretion with age.

Aging↗

Hypothalamic-pituitary function in the old irregularly cycling rat.

Older irregularly cycling and younger regularly cycling rats exhibited similar increases in LH levels 1, 2 and 3 wks after ovariectomy, but FSH reached higher levels in the older than in the younger rats after ovariectomy. Neither the ability of 5 microgram/kg estrogen to suppress gonadotropin levels nor the capability of larger doses of estrogen (250 micrograms/kg) and/or progesterone (10 mg/kg to trigger an LH release were altered with age. LH release from the pituitary in response to exogenous gonadotropin releasing hormone (GnRH) was attenuated in ovariectomized older rats, but was partially restored after estrogen and/or progesterone priming. The FSH levels after GnRH treatment were greater in the estrogen primed aged that in estrogen-primed younger rats. The disruption of regular cycles in older rats may be due to a lack of a neural signal for gonadotropin release rather than a failure of the hypothalamus to respond to the positive feedback effect of estrogen or the failure of the pituitary to respond to GnRH.

Aging↗

Pattern of follicular growth and steroidogenesis in the ovary of aging cycling rats.

Prior to the cessation of reproductive cycles, older female rats exhibit irregular and prolonged cycles due to alterations in the hypothalamic-pituitary-ovarian axis. In order to evaluate the age-related changes in the ovary, the histology, and estradiol, testosterone and progesterone concentrations within the ovaries of mature regular cycling (4--5 mo. old) and older irregular cycling (10--11 mo. old) rats were examined. At estrus, the number of non-atretic growing follicles (150--300u in diameter) was greater in the mature than in the older rats (18 +/- 1.5 vs 4.5 +/- 1.4). However, the number of preovulatory follicles on proestrus did not differ (6.0 +/- 1.2 vs 5.5 +/- 0.6). Estradiol, testosterone and progesterone concentrations on proestrus in mature rats averaged 38.8 pg, 56.1 pg, and 1.0 ng/ml of ovary, respectively. In the older proestrous rat, only estradiol was altered, increasing to 124.3 pg/mg. In addition, many of the preovulatory follicles within the aged ovary were larger (greater than 600u in diameter) than those within the mature ovary. On the day of estrus virtually all preovulatory follicles ovulated in the mature rat, whereas large follicles, less than or equal to 600u in diameter, remained in the older ovary. In addition, estradiol levels remained elevated and ovarian cysts were observed in the aged ovary. Thus, in the older irregular cycling rat, 1) pre-ovulatory follicles develop, but many do not ovulate; 2) these non-ovulatory follicles form ovarian cysts which remain within the ovary. The number of cysts may increase with age until a polycystic ovary develops and the rat enters a constant estrous state.

Aging↗

Gonadotropin binding and testicular function in old rats.

Serum testosterone levels, testicular LH binding and the spermatogenic cycle were analyzed in rats 4 and 22 mo of age. With age, serum testosterone levels decreased from 3.2 to 0.63 ng/ml serum. There was no age related decline in testicular LH binding or changes in the spermatogenic cycle.

Aging↗

Patterns of sex steroid and gonadotropin secretion in aging female rats.

Serum estradiol, progesterone, LH, and FSH were determined by RIA in 20- to 30-month-old constant estrous (CE), irregular pseudopregnant (PP), and anestrous (AS) female rats and from 4- to 5-month-old cycling female rats. Disruption of the estrous cycle in aging rats was associated with major changes in secretion of pituitary gonadotropins and ovarian steroids. None of the old rats, in contrast to the young rats, showed cyclic changes in any of the hormones studied. Serum progesterone was much higher in the PP than in the other two old groups, serum estradiol averaged somewhat higher in the CE than in the other two aged groups, and all four hormones were lower in the AS rats than in any other group. Basal serum FSH values were higher in the old CE rats than in either of the other old age groups and were slightly higher than in young rats on the afternoon of proestrus or morning of estrus. Serum FSH values were lower in the old PP and AS rats than in young rats on the afternoon of proestrus or morning of estrus. Serum FSH values were lower in the old PP and AS rats than in young rats on the afternoon of proestrus or morning of estrus. Serum values in the old CE rats were about the same as in young rats on the morning of proestrus or estrus, about the same in old PP rats as in young rats during diestrus, and were undectable in old AS rats. Since the ovaries of old rats are capable of near normal function under appropriate gonadotropic stimulation, it is concluded that the major cause for cessation of regular estrous cycles in old rats lies in altered hypothalamo-pituitary function.

Aging↗

Gonadotrophin regulation in the lactating rat.

Post-partum lactation in the rat is associated with follicular quiescence and an attenuation of gonadotrophin secretion. The present study demonstrates that the lactating rat responds to exogenous LH-releasing hormone (LH-RH) in a manner similar to dioestrous rats. Oestrogen priming increases the LH and FSH response to LH-RH to a smaller degree in ovariectomized, lactating, than in non-lactating, ovariectomized rats. Pituitary LH levels throughout lactation did not seem to be related LH-RH-induced LH release. A diminished post-castration rise in both LH and FSH, and a diminished positive feedback response to oestrogen administration were also observed and may indicate a disruption of gonadotrophin regulation at both the hypothalamic and the pituitary level.

Animals↗

Role of FSH in regulating granulosa cell division and follicular atresia in rats.

The effects of PMSG on the mitotic activity of granulosa cells and atresia of large folicles in 24-day-old rats were examined. The results showed that the labelling index (1) decreased in atretic follicles parallel with a loss of FSH binding, and (2) increased in hypophysectomized rats treated with FSH. It is concluded that FSH stimulates granulosa cell divisions and that atresia may be caused by reduced binding of FSH to the granulosa cells.

Animals↗