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4.4 - 4th November 1998


Hypothalamic control of development and aging of the thymus.

Hirokawa K; Utsuyama M; Kobayashi S

Department of Pathology and Immunology, School of Medicine, Tokyo Medical and Dental University, Japan.

Mech Ageing Dev, 100(2):177-85 1998 Jan 30

Removal of pituitary gland results in atrophy of the thymus. As the pituitary gland is under the control of the hypothalamus, destruction of the anterior portion of the hypothalamus (AHTL) is expected to negatively influence the thymic function. Contrary to our expectation, the thymus became hypertrophic and the serum level of the growth hormone (GH) markedly increased, when the anterior portion of the hypothalamus was widely destroyed in rats at 1 month and over. The results suggested that AHTL removed the cells secreting GHRIH (growth hormone release inhibitory hormone), but not GHRH (growth hormone releasing hormone), leading to increased secretion of GH from pituitary gland and thymic hyperplasia. In other words, the development and aging of thymus appears to be under the balance of the positive (GHRH) and negative (GHRIH) signals of the hypothalamus. It is most likely that the positive signal is high just after the birth and decreases thereafter with a concomitant increase of the negative signal, leading to the onset of thymic atrophy at around puberty.

Reproductive aging in the Djungarian hamster, Phodopus campbelli.

Edwards HE; Tweedie CJ; Terranova PF; Lisk RD; Wynne-Edwards KE

Department of Biology, Queen's University, Kingston, Ontario, Canada.

Biol Reprod, 58(3):842-8 1998 Mar

Changes in fertility (delivery success), fecundity (litter size and weaning success), sensitivity to pregnancy-blocking stimuli (mate removal after 24 h), and hypothalamic-pituitary-ovarian function were assessed during reproductive aging in the Djungarian hamster, Phodopus campbelli. All indices of aging occurred earlier in the Djungarian hamster than they do in other laboratory models, including the mouse. Fertility and fecundity were halved by 8 mo of age, and the response to pregnancy-blocking stimuli disappeared by 4-6 mo. Pup birth weight increased with maternal age and decreasing litter size. Older females also tended to lose entire litters rather than to reduce litter size and successfully wean remaining pups. Impaired ovarian function was a major contributor to reproductive aging. Numbers of large antral follicles developing in aged females and in aged females receiving eCG treatment were similar to those in young females. However, a few preovulatory follicles routinely failed to ovulate from each ovary. Healthy preovulatory follicles in old females secreted the large quantities of estradiol-17 beta typical of estrous cycles, but eCG-induced preovulatory follicles did not. As young females of this species have smaller folicular reserves than other rodent species, and follicle numbers in older females are further reduced (with a high incidence of completely degenerate ovaries), follicular exhaustion was coincident with reproductive failure. Neuroendocrine aging of the hypothalamus was also implicated in the loss of a pregnancy-blocking response and the failure of maternal care with increasing maternal age. Similarities to reproductive aging in long-cycle species (including primates) suggest that the Djungarian hamster is a useful laboratory model that deserves further investigation.

Effects of aging and gonadal failure on the hypothalamic-pituitary axis in women.

Santoro N; Banwell T; Tortoriello D; Lieman H; Adel T; Skurnick J

Department of Obstetrics and Gynecology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103-2757, USA.

Am J Obstet Gynecol, 178(4):732-41 1998 Apr

OBJECTIVE: Our aim was to determine the effect of aging on the hypothalamic-pituitary-gonadal axis function. STUDY DESIGN: We studied 9 women aged 25 to 40 years with well-defined idiopathic premature ovarian failure and compared them with 8 women aged 51 to 70 years who had age-appropriate menopause. All women underwent 24 hours of frequent blood sampling every 10 minutes before and after replacement with transdermal estradiol targeted to achieve serum concentrations of approximately 100 pg/ml. RESULTS: In the absence of estrogen exposure, women with premature ovarian failure demonstrated a greater 24-hour mean luteinizing hormone concentration compared with that in the older women with age-appropriate menopause (32.3+/-4.3 mlU/ml vs 19.2+/-2.4 mlU/ml, p=0.0001). Despite the lesser luteinizing hormone serum levels in the older group, the luteinizing hormone pulse frequency per 24 hours was similar (22.1+/-3.0 pulses per 24 hours in prematurely menopausal women vs 21.9+/-2.5 pulses per 24 hours in the older postmenopausal women, p=0.94). When exposed to estrogen, mean luteinizing hormone concentrations decreased to 11.6+/-2.7 mlU/ml in prematurely menopausal women versus 4.4+/-1.0 mlU/ml in older postmenopausal women, p=0.017. Both groups had suppressed mean luteinizing hormone secretion compared with their paired, non-estradiol-exposed studies, p=0.0001. Frequency of luteinizing hormone pulsations was reduced to 16.5+/-3.5 pulses per 24 hours in prematurely menopausal women exposed to estradiol (p < 0.0058, compared with non-estradiol-exposed women). Further reduction was observed in older postmenopausal women (11.5+/-1.1 pulses per 24 hours, p=0.0001, compared with nonestradiol exposure, and p=0.0125, vs prematurely menopausal, estradiol-exposed women). Pulse amplitude was suppressed in both prematurely menopausal women (5.6+/-0.5 mlU/ml to 2.3+/-0.5 mlU/ml, p=0.0001) and older postmenopausal women (3.6+/-0.4 mlU/ml to 2.3+/-0.6 mlU/ml p=0.04) in the presence of estradiol. Although luteinizing hormone pulse amplitudes were greater in the women with premature menopause in the absence of estradiol (p=0.0028) compared with those in older postmenopausal women, pulse amplitudes became similar in the presence of estradiol. Parallel changes in mean follicle-stimulating hormone were observed. Women with premature ovarian failure had a mean follicle-stimulating hormone level of 71.1+/-9.4 mlU/ml that was suppressed to 18.0+/-4.1 mlU/ml after estradiol exposure (p=0.0001); values in older postmenopausal women were 45.9+/-6.0 and 10.3+/-2.0, respectively (p=0.0001). Although the women with premature ovarian failure secreted more follicle-stimulating hormone in the absence and presence of estradiol, only the former situation was statistically significant (p=0.0008 and p=0.23, respectively). CONCLUSIONS: These data suggest that there is an age-related decrease in gonadotropin secretion that may be hypothalamic or pituitary in origin. There is less luteinizing hormone secreted in women older than age 50. There is greater suppression of luteinizing hormone and follicle-stimulating hormone secretion by estradiol in aged women. Thus these data indicate that postmenopausal hormone changes involve central hypothalamic-pituitary alterations, as well as ovarian changes.

Lifespan changes in the human hypothalamus.

Hofman MA

Netherlands Institute for Brain Research, Graduate School of Neurosciences, Amsterdam, The Netherlands.

Exp Gerontol, 32(4-5):559-75 1997 Jul-Oct

The various cell groups in the human hypothalamus show different patterns of aging, which are the basis for changes in biological rhythms, hormone production, autonomic functions, and behavior. The suprachiasmatic nucleus (SCN), the clock of the brain, exhibits circadian and seasonal rhythms in vasopressin synthesis that are disrupted later in life. Furthermore, the age-related sexual differences in the number of vasoactive intestinal polypeptide neurons in this nucleus reinforces the idea that the SCN is not only involved in the timing of circadian rhythms but also in the temporal organization of reproductive functions. The sexually dimorphic nucleus of the preoptic are (SDN-POA), or intermediate nucleus, is twice as large in men as in women, a difference that arises between the ages of two to four years and puberty. During aging a dramatic, sex-dependent decrease in cell number occurs, leading to values which are only 10-15% of the cell number found in early childhood. The vasopressin and oxytocin producing cells in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) are examples of neuron populations that seem to stay perfectly intact in old age. Parvocellular corticotropin-releasing hormone-containing neurons are found throughout the PVN and are even activated in the course of aging, as indicated by their increase in number and by their coexpression with vasopressin. Part of the arcuate nucleus of the hypothalamus (ARH), or tubero-infundibular nucleus, contains hypertrophic neurons in postmenopausal women. These hypertrophied neurons contain neurokinin-B, substance P, and estrogen receptors and probably act on LHRH neurons as interneurons. The tuberal lateral nucleus (NTL), involved in feeding behavior and energy metabolism, does not show any neuronal loss in senescence. These findings indicate that each cell group of the human hypothalamus has its own sex-specific pattern of aging. In fact, some hypothalamic nuclei show a dramatic functional decline with aging, whereas others seem to become more active later in life.



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