The majority of seasonally breeding mammals show a seasonal pattern of prolactin secretion with peak concentrations in spring or summer and a nadir in autumn or winter. Photoperiod influences prolactin secretion via its effects on the secretion of the pineal hormone melatonin. Preliminary evidence suggests that the effects of melatonin on both prolactin and gonadotrophin secretion are via a common target area, possibly within the anterior hypothalamus, and that differences in response to photoperiod may be due to differences in the processing and/or interpretation of the melatonin signal. In contrast to seasonal gonadotrophin secretion, the seasonal changes in prolactin are not due to changes in the sensitivity of a feedback loop and so must be due to direct effects on the hypothalamic pathways that control prolactin secretion. Little else can be said with confidence about the neuroendocrine mechanisms that lead to the seasonal changes in prolactin secretion. Dopamine and noradrenaline turnover in the arcuate nucleus and median eminence decrease under short daylength. If catecholamine turnover in these structures is positively correlated with catecholamine concentrations in the long or short hypophysial portal vessels, it is unlikely that the decrease in prolactin concentration in winter is due to the effects of increased concentrations of dopamine or noradrenaline in the portal vessels. There is, however, evidence for increased pituitary sensitivity to dopamine under short daylength, so increased dopamine concentrations may not be required for suppression of prolactin secretion at this time. In addition to the diminished secretion of prolactin under short daylength, rate of prolactin synthesis and pituitary content of prolactin also decline although the mechanisms that regulate these changes are poorly understood. Although all seasonal breeders show a seasonal change in prolactin secretion, there are continuously breeding species in which prolactin secretion is also under photoperiodic control. It is likely therefore that a seasonal pattern of prolactin secretion is only evidence of neuroendocrine sensitivity to changing photoperiod. Depending upon the species, this sensitivity to the seasonal changes in daylength may or may not be accompanied by seasonal changes in a biological endpoint such as seasonal reproduction or indeed other adaptations. Whether the seasonal change in prolactin secretion is an endocrine mediator of such adaptations remains in contention. Certainly in some species this signal does have a role in reproduction. For example, in species with an obligate seasonal embryonic diapause, the seasonal increase in prolactin can act as a luteotrophin (mink and western spotted skunk) or luteostatin (Bennett's and tammar wallabies.(ABSTRACT TRUNCATED AT 400 WORDS)

Seasonal prolactin secretion and its role in seasonal reproduction: a review.

The Pineal Control of Aging

Seasonal cycles were monitored in groups of wild (mouflon), feral (Soay) and domesticated breeds of sheep (Shetland, Blackface, Herdwick, Norfolk, Wiltshire, Portland, Merino, Soay x Portland and Soay x Merino) living outdoors near Edinburgh (56 degrees N). Changes in the blood plasma concentrations of prolactin and FSH, and growth of the horns and pelage were measured every half calendar month from 1 to 3 years of age. In all breeds there was a clearly defined seasonal cycle in the plasma concentration of prolactin with an 18-66-fold increase in mean values from the nadir in November and December to the peak in May and June. The seasonal increase in prolactin was closely correlated with the seasonal increase in the growth of the horns, both within and between breeds (e.g. time of peak prolactin vs horn growth for 11 breeds, R = 0.62, P less than 0.05). In the mouflon, Soay and some of the domesticated breeds of sheep (Wiltshire, Herdwick and Shetland), the seasonal increase in prolactin was also temporally correlated with the resurgence of growth of the pelage in spring and a conspicuous moult. In the other breeds developed to produce fine wool (e.g. Norfolk, Portland and Merino), there was no clear seasonal change in the pelage and growth continued throughout the year. Comparison between breeds indicated that continuous growth of the pelage was associated with higher plasma prolactin concentrations in winter. The times of the seasonal changes in plasma concentrations of prolactin were not significantly correlated with the corresponding changes in the plasma concentrations of FSH. The overall results are consistent with a role for prolactin related to the growth of the horns and pelage rather than the seasonal cycle in reproduction. The differences between the wild-type and the domesticated breeds in the pelage represent the effect of selective breeding to produce a long fine fleece which has involved changes in both the seasonal pattern of prolactin secretion and the growth characteristics of the hair fibres.

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Correlation with changes in horns and pelage, but not reproduction, of seasonal cycles in the secretion of prolactin in rams of wild, feral and domesticated breeds of sheep.

For more than 50 years, Parkinson's disease (PD) has been conceptualized as a product of nigro-striatal dopamine (NSD) system degeneration. In spite of a growing body of evidence depicting the mammalian brain as an interrelated complexity of circuitous systems, dopamine (DA) deficiency of the NSD is still regarded as the main problem, with DA replacement being the purpose of therapeutic intervention. For at least 191 years circadian involvement in various aspects of PD, including depression and insomnia, has been recognized as an integral part of the symptom matrix of PD and yet attempts to elucidate the involvement of this system is uncharted territory. The present review attempts a major reorganization of mammalian brain into a coordinated complex involving the NSD and the retinal hypothalamic tract (RHT) as the primary systems involved in the retino-diencephalic/mesencephalic-pineal (RDMP) axis. Secondary systems including the lateral hypothalamus (LH), the area postraema (AP) and the subthalamic nucleus (STN) also form an integral part of this system as they have been shown to be either intimately related to the primary systems of the RDMP axis or have been shown to be significantly involved in the expression and treatment of PD. A large volume of evidence suggests that the RDMP axis is activated during the course of PD and during therapeutic intervention. Four types of neurotoxicity associated with melatonin are identified and the susceptibility of various parts of the RDMP axis to undergo neuropathological change, the tendency for melatonin to induce PD-like behavioural toxicity, and the relationship of this to PD symptomotology are described. This includes adverse effects of melatonin on motor function, hypotension, the adjuvant use of benzodiazepines, depression, insomnia, body weight regulation and various biochemical effects of melatonin administration: all problems currently facing the proposal to introduce melatonin as an adjuvant. It is suggested further that traditional DA replacement may well work by exerting its effect upon the circadian system, rather than simply replacing deficient DA. Activation of the circadian function by antagonizing melatonin with bright light not only has therapeutic value in treating the primary symptoms of PD but it shares a common mechanism with L-dopa in reducing the occurrence of seborrheic dermatitis. Concepts at the centre of understanding pineal function in PD, including pineal calcification, melatonin deficiency, symptomatic versus protective features of melatonin and antioxidative effects, are explained in a counterintuitive context. Intriguing propositions including the role of the retina in the aetiology of PD and that the nigra functions as a retina in this disorder are presented with the intention to provide a new understanding of the underlying compromised function in PD and to provide new treatment strategies. For the first time, abundant evidence is presented describing PD as an endocrine disorder of melatonin hyperplasia. The role of circadian interventive therapies and internal desynchrony in the aetiology and progression of PD provides a new direction for understanding the underlying physiology of a disease which is currently in a state of impasse and provides new hope for those who suffer from its debilitating effects.

Parkinson's disease as a neuroendocrine disorder of circadian function: dopamine-melatonin imbalance and the visual system in the genesis and progression of the degenerative process.

Hypothalamo-pituitary disconnected (HPD) and control Soay rams were treated chronically for 48 wk with s.c., continuous-release implants of melatonin while under long days (16L:8D). The implants produced continuously elevated blood concentrations of melatonin 2-3 times higher than the normal nocturnal maximum. The long-term treatment induced a biphasic effect on prolactin secretion in both the HPD and control rams, with a marked decrease in the blood prolactin concentrations for 10 wk followed by a gradual increase. The introduction of a second melatonin implant after 20 wk failed to affect prolactin secretion. The treatment with melatonin also caused a dynamic effect on FSH secretion, but this occurred in the control rams only. Blood concentrations of FSH in the HPD rams were very low throughout, but there were minor changes in testicular diameter that were correlated with variations in prolactin. Overall, the results support the conclusion that 1) melatonin acts primarily in the pituitary gland to affect prolactin secretion, and partial refractoriness develops at this level for control of prolactin; and 2) melatonin acts most probably in the hypothalamus to affect gonadotropin secretion, and refractoriness develops at the level of the neural tissue regulating GnRH release for control of gonadotropins.

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Refractoriness to a static melatonin signal develops in the pituitary gland for the control of prolactin secretion in the ram.

Experiments in minks, as in a number of other seasonal breeders, clearly demonstrate that the pineal gland is essential for the photoperiodic control of reproduction. While maintenance of pineal-intact minks under natural photoperiods results in a set of seasonally appropriate changes in testicular activity, pinealectomized minks undergo none of these changes but rather remain sexually inactive as under long-day conditions. Thus, the consequences of pinealectomy differ from one photoperiodic species to another, but the unifying feature is the organism's need for the pineal gland to respond appropriately to changes in day length.



Although the precise mechanism by which the pineal regulates hypothalamic-pituitary gonadal function remains unknown, the results of the present study indicate that, in the mink, luteinizing hormone-releasing hormone axonal transport is affected by pinealectomy.



Furthermore, our results suggest that the pineal does not act exclusively upon the neuroendocrine-gonadal system but also acts on other functions that are influenced by photoperiod. Pinealectomized minks left in natural conditions cannot adjust their prolactin secretion in response to either long or short photoperiods. Operated animals continued to have plasma prolactin variations but at irregular intervals and with no apparent relation to the time of the year. The data strengthen the hypothesis that melatonin may act at some point on the hypothalamic neuroendocrine systems, which regulate the two functions differently, and that melatonin is not an anti- or progonadal substance but rather a seasonal transducer.

Long-term effects of pinealectomy on testicular function, luteinizing hormone-releasing hormone hypothalamic system, and plasma prolactin levels in the mink, a short-day breeder.

A. Lacroix

Papers

Long-term effects of pinealectomy on testicular function, luteinizing hormone-releasing hormone hypothalamic system, and plasma prolactin levels in the mink, a short-day breeder.