COMMENTS ON J. ARIENS KAPPERS' REVIEW AND OBSERVATIONS ON PINEAL ACTIVITY
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A M . ZOOLOGIST, 4:53-57 (1964).
COMMENTS ON J. ARIENS KAPPERS' REVIEW AND
OBSERVATIONS ON PINEAL ACTIVITY
WILLARD D. ROTH
Department of Anatomy, Harvard Medical School
Harvard University
[The author was a discussant in the elsewhere. Ablation of the pineal gland in
symposium on recent advances in neuro- prepubertal males gives the results shown
anatomy, held at the XVlth International in Table 1. In this case—where the animals
Congress of Zoology. The author therefore were housed together to equalize any pos-
has combined comment on Dr. Kappers' sible effects of unrecognized environmental
paper with additional studies. See J. Ariens variables—the only measured effects of epi-
Kappers. 1964. Survey of the innervation physeal ablation or injection of pineal ex-
of the pineal organ in vertebrates. Am. tracts are on the weight of the seminal
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Zoologist, this issue.—Editor.] vesicles and ventral prostates. These results
Professor Ariens Kappers is to be con- are quite significant when analyzed sta-
gratulated both for his courage and his tistically. Several other workers have re-
skill in presenting in only twenty minutes ported similar results, especially Thieblot
such a complete review of recent work on and his colleagues (Thieblot and Blaise,
the mammalian pineal organ. His cover- 1962), who obtained an effect on testicular
age has been discriminating as well as weight as well. Thus all of the recent
thorough; there can be no significant ob- papers show changes following pinealec-
jection to either his facts or his conclusions. tomy which unquestionably are statistically
In discussing his paper, therefore, I shall significant, but the magnitude of their bio-
amplify some of his points with the in- logical significance remains problematical.
tention of stimulating speculation and, The pineal organ clearly exerts some sort
hopefully, of engendering some novel of influence on the degree of development
thoughts and directions of research on the of the various components of the mam-
epiphyseal complex in vertebrates. To this malian reproductive system. But is this
end, I would like to communicate some a direct, primary effect, or is it merely an
results we have obtained in studying the indirect effect of little importance in nor-
rat pineal organ which, in my opinion, are mal gonadal development?
directly pertinent to the present discussion. Obviously, the pineal is not essential to
First I would like to comment on Dr. life or even to normal growth in the rat.
Kappers' remarks concerning a functional It seems neither to be necessary in gonadal
relationship between the pineal organ and differentiation nor indispensable to normal
the reproductive system. Numerous reports reproductive processes. The pineal organ
appear in the literature of an inhibitory does not exert a prepotent control of the
effect of the pineal organ on the develop- development of the reproductive system;
ment of gonads and accessory reproductive rather it participates in regulating the in-
structures. This effect now seems to be terrelationships of different parts of the
fairly well documented, at least in the case system to each other and/or to other parts
of female rats. Recently we have observed of the endocrine system. Much the same
a similar inhibiting effect in male rats dur- could probably be said concerning the re-
ing puberty. A complete description of the ports of an epiphyseal-thyroid relationship
experimental procedures and results of this
or an epiphyseal-adrenal axis. The rat with-
study is being submitted for publication
out a pineal organ certainly is not in acute
The speaker's studies on the rat pineal cited in endocrinological distress, but is rather in
this discussion were supported by Grant A2943C-2
of the USPHS and by a grant from the Boston Medi- a subtle condition of physiological malad-
cal Foundation, Boston, Massachusetts. justment.
(53)54 WILLARD D. ROTH
TABLE 1. Effects of pinealectomy in male rats 6 weeks after operation
TREATMENT N WEIGHT SEMINAL VENTRAL ADRENALS TESTES
fern) VESICLES PROSTATE
(mgm/100 gm body weight)
CONTROL 33 357 ± 30 120 ± 18 103 ± 16 13.6 ±1.7 958 ± 89
SHAM
PINEALECTOMY
15 350 ± 31 117 ± 18 95 ±12 13.5 ±1.5 935 ± 80
PINEALECTOMY 28 356 ± 28 145 ± 25* 120 + 23** 13.8 + 2.1 949 + 103
PINEALECTOMY
+ SALINE
10 368 129 143 ± 30 120 ±27** 13.4 + 1.5 927 + 80
PINEALECTOMY
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+PINEAL EXTRACT 10 356 ± 42 132 * 25 113 ± 15 14.1± 2.2 941 ± 121
* Seminal vesicles 22% > controls, P controls, PPINEAL ACTIVITY 55
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FIG. 1 and 2. Pineal parenchymal cells from an animal in constant light (Fig. 1), and from an
animal in constant darkness (Fig. 2). Note the greater volume of the cells in Fig. 2, as indicated
by spacing of the nuclei, and the appearance of prominent nucleoli in nearly all nuclei as con-
trasted with those in Fig. 1. (Hematoxylin and eosin, X300.) (After Roth, Wurtman, and Alt-
schule, 1962, Endocrin.)
inorganic P32 confirmed this fact. Indeed, the animals had been in light or in dark-
the measurements showed the pineal organ ness for four hours. The specific activity
to be several times as active in the rate of of the epiphyses from animals injected at
incorporation of radioactive phosphorus as midnight is approximately 70% higher
the pituitary, adrenal glands, and ovaries, than that of organs from animals injected
and many times more active than brain at noon. There was no overlap in indi-
tissue. In addition, we noted a variation vidual measurements between the two
in the metabolic activity of the pineal groups. The posterior pituitary also shows
organ which seemed roughly correlated an elevated activity in darkness, but the
with time of day at which the phosphorus change is less than that shown by the
was injected. Exercising considerable care pineal organ. The anterior pituitary gland
in procedure and evaluating the metabolic shows no change. Table 3 shows similar
activity in terms of specific activity based measurements for prepubertal females in-
on counts per minute per microgram of
phosphorus, we found a clear difference TABLE 2. Comparison of specific activities day and
between day and night values in activity night
of the pineal organs. A complete descrip- TIME INJECTED N PINEAL POSTERIOR
PITUITARY
ANTERIOR
PITUITARY
tion of the experimental methods and
results of the study of the circadial varia- 12:00 19 23S ± 25 123 ± 20 74 ± 12
In Ufiht 4 hours (N = 18)
tion in metabolic activity of the rat pineal
as shown by the rate of P32 incorporation 24:00 IS 391 i 23 172 * 23 .79 i 14
is being submitted for publication else- In dark 4 hours (N - 17)
where. P «0.001 P 0.3
Table 2 summarizes the measurements
made, in prepubertal males into which the Prepubertal males 26 days old (65 gin). Counta per minute per
microgram phosphorus, 2 - 2 , 5 hours after injection with SO micro-
radioactive phosphorus -was injected after curies P 3 2 . ' ' . " .56 WILLARD D. ROTH
TABLE 3. Comparison of specific activities day and These findings, in my opinion, make
night doubly important the elegant work of Kap-
TIME INJECTED N PINEAL POSTERIOR
PITUITARY
ANTERIOR
PITUITARY
pers (1960) on the innervation of the mam-
malian pineal organ. As he has pointed
S 00 - 13:00 14 232*46 95 ±16 63 +12 out, the pineal receives a heavy orthosym-
Light
pathetic innervation from the superior cer-
18:00 - 2.00 IS 391 + 134 147 4 49 59 ± 12
vical ganglia. This innervation, coming
Dark (N = 14) via the nervi conarii, constitutes most of
P«0.01 P0. 3
the pineal nerve supply. It is known, of
course, that the superior cervical ganglia
Prepubertal females 26 days old (65 gin). Counts per minute per respond to changes in external illumina-
microgram phosphorus, 2-2.5 hours after injection with 40 micro-
curies P**2. Counts multiplied by 1.2 for comparison with male data. tion of the retina. Hence it seems reason-
able to suggest that the nervi conarii con-
jected at various times throughout the stitute a pathway whereby light can exert
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twenty-four hour period. In this experi- an effect on the pineal. This might ac-
ment, food and water were withheld to count for the fact that light does affect
control simple metabolic factors. The vari-
the pineal organ although there is no ap-
ation here is greater, as these figures in-
preciable innervation to it from the brain.
corporate the rise and fall in activity at
different times in the circadian cycle, but In• this regard it should prove interesting
the result is the same as in the previous to measure the results of superior cervical
experiment. The specific activity of pineal ganglionectomy on the metabolic activity
organs during the hours of darkness is of the pineal organ, and on its ability to
nearly 70% higher than during the hours form serotonin, melatonin, and other bio-
of illumination. These effects are not due genic amines it is known to produce. One
to fluctuations in temperature or food in- is curious to know whether removal of the
take. It is unlikely they are a result of ganglia or transection of the nervi conarii
extraneous signals as the animals were in might either abolish or enhance the pineal
a separate room isolated from daily activi- inhibition by light.
ties in the general animal rooms. Conse- In addition, these findings on mamma-
quently it seems a tenable working hypo- lian pineal innervalion make it possible to
thesis to assume that the pineal organ is seek generalizations concerning the epi-
responding in a fairly direct way to illum- physeal complex throughout the verte-
ination. Again it appears that the effect brates. The rat, on which most of the
of the light is an inhibitory one. In any modern work has been done, is primarily
case it seems clear that the rat pineal organ a nocturnal, continuously reproducing spe-
is metabolically more active during the cies. Studies of diurnal mammals or of
night than during the day, and it will be forms showing marked seasonal reproduc-
necessary to consider this rhythm in future tive habits relative to the length of day-
experiments on epiphyseal physiology and light might add much to our understand-
biochemistry. Past experiments attempting ing. Also, though Dr. Kappers has, very
to demonstrate a feedback inhibition of properly, emphasized the great morpho-
the pineal by injection of hormones or logical differences between the light-recep-
pineal extracts may have failed because tor epiphyseal organs of fishes and am-
measurements were made during the day, phibia and the gland-like parenchymal
when the pineal was already strongly in- pineal organs of birds and mammals, it
hibited. It also indicates that experiments might be useful to look for similarities in
designed to test physiological effects of the the two types as well. Thus it now appears
pineal organ in whole animals should be that both types of organs show a response
carefully controlled with regard to the to external illumination. Perhaps the ob-
daily photoperiod. vious morphological differences reflectPINEAL ACTIVITY 57
more a change in the way that information new findings do, however, make it possible
about external illumination is transmitted to formulate much more precise hypotheses
to the epiphyseal region than a total and about its function and permit the design
unrelated change in function. On the of carefully planned, explicitly controlled
other hand, Oksche and Vaupel-von Har- experiments to test these hypotheses.
nack (1963) have presented evidence, based Therefore it seems possible that this organ
on studies of fine structure, that secretion will not much longer remain the enigma
as well as photoreception may occur in it has been for so many confusing years.
parts of frog pineal organs. If substanti-
ated by further work, this would suggest REFERENCES
another, possibly more important, simi- Fiske, V. M., J. Pound, and J. Putnam. 1962. Effect
larity in function between the two major of light on the weight of the pineal organ in
types of epiphyseal organs. A careful mor- hypophysectomized, gonadectomized, adrenalecto-
phological study of the much neglected mized or thiouracil fed rats. Endocrin. 71:130-133.
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epiphyseal region in reptiles could prove Kappers, J. Ariens. 1960. The development, topo-
valuable in this connection. graphical relations and innervation of the epi-
physis cerebri in the albino rat. Z. Zellforsch. 52:
In summary, it must be admitted that 163-215.
none of these exciting new findings yet Oksche, A., and M. Vaupel-von Harnack. 1963.
answers the central question as to the func- Comparative election microscopic studies of the
tion of the mammalian pineal, although pineal organ. International round-table confer-
ence on the epiphysis cerebri. Amsterdam, July
they do seem to make it more unlikely than 10-13, 1963. (In press)
ever that it is the seat of the soul. We Quay, W. B. 1961. Reduction of mammalian pineal
must agree with Dr. Ariens Kappers in his weight and lipid during continuous light. J. Gen.
contention that the mammalian pineal or- Comp. Endocrin. 1:211-217.
gan "—far from being a mere phylogenetic Roth, W. D., R. J. Wurtman, and M. D. Altschule.
non-functional relic, is a veritable factory 1962. Morphologic changes in the pineal paren-
working at a high metabolic rate and pro- chyma cells of rats exposed to continuous light or
darkness. Endocrin. 71:888-892.
ducing a number of compounds—", but we
Thieblot, L.. and S. Blaise. 1963. Influence de la
are still sore beset to explain exactly why glande pineale sur les gonades. Ann. d'Endocrin.
or at what it is working so hard. These 24:270-286.Downloaded from http://az.oxfordjournals.org/ by guest on November 9, 2015
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