Reproductive function of melatonin

MELATONIN REVIEW: REPRODUCTIVE
SYSTEM

INTRODUCTION

Epiphysis Cerebri also known as the Pineal gland produces the hormone melatonin in 1955 Lerner & Y.Takahashi first developed a so-called bioassay for melatonin determination based on a qualification of frog skin blanching (1)


(Melatonin Structure)
.
Now melatonin is considered a hormone ( N- acetyl- 5 methoxy tryptamine) produced especially at night in pineal gland. Its secretion is stimulated by dark and inhibited by light, which takes place in the pinealocytes, the cellular unit of the pineal gland.
Tryptophan is converted to serotonin and finally converted to melatonin, which is an Indole.
Melatonin is metabolized to 6- hydroxyl- mel in the liver and the main metabolite excreted is 6-sulphatoxy-mel and this excretion urinary component is helpful in assessing pineal gland function especially in children (2) .
Melatonin is a ubiquitous natural neurotransmitter involved in numerous aspects of biological and physiological regulation of body functions. The role of endogenous melatonin in circulation rhythm disturbances and sleep disorders is well established. Melatonin has been shown to modify immunity, the stress response, reproductive physiology and also certain aspects of the aging process.

Melatonin and Human Puberty

Shortly after birth very little melatonin or aMT6s is detectable in body fluids. A robust melatonin rhythm appears around 6 to 8 weeks of life. The plasma concentration increases rapidly there after and reaches a lifetime peak on average at 3 to 5 years old. The increment is much greater at night. Subsequently a steady decrease is seen, reaching mean adult concentration in mid to late teens with the major decline occurring before puberty. Values remain relatively unchanged until 35 to 40 years, and a final decline in amplitude then takes place until low levels are seen in old age (3) . Exceptionally healthy elderly may not show this age related decline.
The precise mechanism controlling the onset of puberty are not fully known yet. The maturing of ovaries and/or testes is triggered by secretion of the hormone FSH and/ or LH from the pituitary. In turn, this pituitary function is dependent on GnRH secretion from the hypothalamus, a central control unit of the brain. But, ultimately, we do not know what triggers the function of the hypothalamus with regard to puberty. A possible candidate is melatonin, since ther is strong decline of nocturnal concentrations of the hormones particularly before and during puberty. Thus it is hypothesized that high level melatonin inhibits hypothalamus function in humans (4).

Melatonin as Contraceptives


The effect of melatonin on the hypothalamus pituitary axis and therefore the reproductive system have initiated studied aimed at the use of melatonin as an oral contraceptive (5). When using high doses of melatonin (75 & 300mg daily) in combination with norethisterone, no peak in LH secretion was observed during the menstrual cycle. Furthermore, plasma FSH levels remained constant. These circumstances prevented ovulation and the increase in progesterone during luteal phase. The suggested mechanism of action were antigonadotropic effects on the hypothalamus, such as alteration in the hypothalamic pulsatile GnRH secretion and/ or effects on the pituitary release of LH, or even a direct effect on the ovary. Due to melatonin’s side effects (especially sleep induction, etc.) this possibility now is seen rather skeptically (6).

Melatonin for Infertility

Melatonin may be a key factor in the regulation of seasonal variation in gonadal activity. Exposure to bright light, suppressing the concentration
Of melatonin in circulation, is hypothesized to be useful in treatment of
Both male and female infertility in couples with abnormal melatonin metabolism (7).

Melatonin as a Regime for Cancer

A long photoperiod results in depressed melatonin secretion during the night. In animals, melatonin inhibits the incidence of chemically induced tumors, which is increased by pineal suppression (long light phase) or pinealectomy (8). Pinealectomy stimulates and/ or melatonin inhibits the growth and sometimes the metastasis of experimental cancers of the lung, liver, ovary, pituitary, and prostate as well as melanoma and leukemia (9).
Clinical evidence suggests a role for melatonin in the prevention and even the treatment of Breast cancer (10). The circadian amplitude of melatonin was reduced by more than 50% in patients with Breast cancer vs. patients with nonmalignant breast disease (11). A high melatonin levels have been found in morning urine samples of breast cancer patients, suggesting circadian disorganization. Melatonin down regulates estrogen receptors; inhibits estrogen- stimulated, breast cancer growth; and complements the oncostatic action of antiestrogen drugs (Tamoxifen), leading to the suggestion that melatonin is a ‘natural antiestrogen’ (12). A synergy has been demonstrated between melatonin and all- trans- retinoic acid (ATRA), allowing the use of lower doses of ATRA and thus avoiding its adverse effects (13) .
Anisimov and coworkers (14) have found that constant treatment with melatonin reduced the incidence and the size of the breast carcinomas as well as lowered the incidence of lung metastasis, but interrupted treatment- promoted, mammary carcinogenesis in transgenic mice. They further observed that the life span of the group receiving interrupted treatment was shorter, however, this outcome could be attributed to the transgenic nature of mice used, but this needs further evaluation.
Melatonin may also be considered to play special role in Prostate. Two-third in patients reduces circadian amplitude of melatonin with prostate cancer as compared with those who have benign prostate disease (11)
In prostatic carcinoma, melatonin exerts complex interaction with androgen receptors and affects intracellular trafficking; melatonin does not affect cell growth in the absence of dihydrotesterone (15) .
Melatonin injections have been found to stimulate tumor growth if given in the morning, have no effect when given in mid afternoon and have retarding effect in the evening (16, 17).


REFRENCESES

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