Kennaway D J, Rowe S A
Department of Obstetrics and Gynaecology, University of Adelaide, South Australia.
J Reprod Fertil Suppl. 1995;49:423-35.
The pineal gland has a major role in the translation of scotophase duration into a hormonal signal by the hormone melatonin. Animals such as sheep, goats and deer use the seasonal variation of this signal to coordinate reproductive behaviour with the environment. Despite intensive research over more than 30 years the site(s) of action of melatonin and the resultant intracellular responses are still not clear. This review discusses recent work that has localized the site of action of melatonin in sheep using administration into the hypothalamus in vivo as well as studies on putative melatonin receptors in the pars tuberalis and brain. There is clear evidence that melatonin acting at the level of the pars tuberalis is involved in the seasonal regulation of prolactin secretion, but the evidence for involvement of the pars tuberalis in seasonal reproduction is not compelling. Localized administration of melatonin to the sheep brain revealed that areas anatomically distinct from the pars tuberalis, the ventromedial and arcuate nuclei, simulated seasonal reproductive changes in rams and ewes. Recent studies on brain melatonin binding sites in our laboratory have shown that an antagonist of tissue transglutaminase, Bacitracin, as well as substrates for the enzyme inhibit binding of melatonin to brain membranes. As a working hypothesis, we propose that pineal melatonin secretion alters seasonal reproduction by interactions with a neural transglutaminase at the synapse of neurones involved in the control of GnRH secretion. Synaptic transglutaminase is implicated in the control of the release of neurotransmitter via the synaptic vesicle associated protein, synapsin 1; activation of transglutaminase results in the covalent modification of synapsin 1 such that vesicles are not released from the cytoskeleton. Seasonal variation in the duration of melatonin secretion may result in similar variations in the duration of suppression and activation of transglutaminase. The resultant changes in transmitter release may then be responsible for the seasonal neuronal plasticity previously observed in GnRH neurones.
松果体在通过褪黑素将暗期时长转化为一种激素信号的过程中发挥着主要作用。绵羊、山羊和鹿等动物利用这种信号的季节性变化来使繁殖行为与环境相协调。尽管经过30多年的深入研究，褪黑素的作用位点以及由此产生的细胞内反应仍不清楚。本综述讨论了最近的研究工作，这些工作通过体内向下丘脑给药以及对结节部和大脑中假定的褪黑素受体的研究，确定了绵羊体内褪黑素的作用位点。有明确证据表明，作用于结节部水平的褪黑素参与了催乳素分泌的季节性调节，但结节部参与季节性繁殖的证据并不确凿。向绵羊大脑局部给药褪黑素表明，与结节部在解剖学上不同的区域，即腹内侧核和弓状核，模拟了公羊和母羊的季节性繁殖变化。我们实验室最近对大脑褪黑素结合位点的研究表明，组织转谷氨酰胺酶的拮抗剂杆菌肽以及该酶的底物会抑制褪黑素与脑膜的结合。作为一个可行的假设，我们提出松果体褪黑素分泌通过与参与促性腺激素释放激素（GnRH）分泌控制的神经元突触处的一种神经转谷氨酰胺酶相互作用来改变季节性繁殖。突触转谷氨酰胺酶通过与突触小泡相关蛋白突触素1有关，参与神经递质释放的控制；转谷氨酰胺酶的激活导致突触素1的共价修饰，从而使小泡无法从细胞骨架中释放出来。褪黑素分泌时长的季节性变化可能导致转谷氨酰胺酶抑制和激活时长出现类似变化。随后神经递质释放的变化可能是先前在GnRH神经元中观察到的季节性神经元可塑性的原因。
