A.M. ZOOLOGIST, 7:K2.">-833 (1967).
Aspects of Parathyroid Physiology in Mammals
Roy V. Talmage
Department of Biology, Rice University, Houston, Texas 77001
SYNorsts. This report summarizes the parameters of parathyroid physiology in the
mammal. Emphasis is given to the part played by this hormone in the processes of
growth and remodelling in bone as well as to its function in the maintenance of a
relatively constant level of ionic calcium in the extracellular fluid. The importance of
phosphate ions has been shown, particularly with respect to their role in the rate of
Ca-transport through the extracellular fluid compartments, and their influence on the
rate of parathyroid secretion. In addition, the inter-relationship of the newly discovered hormone, thyrocalcitonin, is considered. The latter hormone, by suppressing resorption of bone, may have an influence in stabilizing plasma levels of calcium; it also
has a moderate, but long range effect on the rate of bone remodelling. Finally, an
attempt has been made to relate the vast amount of work done with these two hormones in mammals to their phylogenetic development in vertebrates. It is suggested
that the parathyroids developed at the time when the specialization of bone in vertebrates produced a solid structure which was incompatible with the fluid calcium concentration needed for the maintenance of many physiological functions. The parathyroid hormone, by its action to increase the transfer of calcium from bone against a
concentration gradient, permitted these vertebrates to maintain the higher fluid calcium ion concentration needed for the normal functioning of the animal.
Since this report is part of a series of papers dealing with the comparative physiology of the parathyroids, only those aspects of
parathyroid function in mammals will be
covered which the author feels are pertinent
in relating parathyroid action in mammals
to the possible phylogenetic development
of these glands. Although these papers deal
primarily with parathyroid physiology,
some discussion of the possible role of
thyrocalcitonin, the recently discovered
hypocalcemic hormone of the thyroid, will
be included.
Several years ago, a review of parathyroid
physiology started with the statement that
"the primary function of the hormone of
the parathyroid glands is the maintenance
of a constant Ca++ concentration in circulating fluids by the addition of Ca, and
that, at the physiological level, most actions
of the hormone are directed toward this
goal" (Talmage, et al., 1965). This point
may well be taken; however, one can not
look only at plasma calcium levels in studying parathyroid physiology in vertebrates.
The work reported here was aided in part by a
research contract from the Atomic Energy Commission.
Therefore, in the review that follows, emphasis will be placed not only on problems
related to calcium in extracellular fluid,
but also on the importance of the concurrent consideration of phosphate turnover
and the role of parathyroid hormone in
growth and remodelling of bone.
The Need for Parathyroid Hormone:
If one takes plasma from any mammal,
even from the rat which has unusually high
phosphate values, and adds to it small increments of calcium and biphosphate ions,
while maintaining the pH, it is readily
demonstrable that mammalian blood is
undersaturated with these ions. In fact, the
blood of man is only about 50% saturated.
However, if one shakes tertiary calcium
phosphate with plasma, it is possible to
remove all the calcium and phosphate from
the blood. The next step is to substitute
chips of either dead or live bone for the
calcium phosphate salt and incubate these
in plasma from the same species. Results of
this type of experiment for the rat are summarized in Figure 1 (Talmage, I967«). If
the calrium and phosphate content of the
825
826
ROY V. TALMACE
BONE SERUM INCUBATION - 4 HOURS
(RAT)
lo-
TOTAL CALCIUM
gPHOSPHOROUS 08 P04
s'
7-
I
o
o
6-
N
5"
O
O
I
4.
32I-
FIG. 1. Bone Serum Incubation—4 Hours. The with bone chips of the femur of the rat. From
bars represent the calcium values of the plasma usedTalmage (1967a).
as incubation medium before and after incubation
plasma used as the incubation medium is
normal, both these ions are withdrawn by
bone. If, however, the content of these ions
in blood is subnormal, the bone will provide them for the plasma. Because of the
excellent circulation of blood through the
bones of mammals, the same type of withdrawal process is assumed to be occurring
continuously in vivo. In fact, the rapid
drop in blood calcium levels, after parathyroidectomy in mammals with no calcium source from the gut, is considered evidence for this. Neuman and Neuman
(1958) referred to this as the phenomenon
of undersaturation of plasma with respect
to itself and the supersaturation of plasma
with respect to bone.
As the result of such data, the author
suggests that the need for parathyroid hormone in any vertebrate species can be established by incubating bone chips from the
animal in plasma taken from normal members of the same species. If during the incubation, calcium and phosphate are withdrawn from the plasma medium, it is suggested that the species normally requires a
secretion of parathyroid hormone to maintain its levels of plasma calcium. However,
such a postulate requires experimental confirmation. Preliminary tests have been run
using frogs, turtles, a skate, and trout. Of
this group, the frog was the only vertebrate
in which the response was similar to that
depicted in Figure 1. The turtle is unusual
because the large carapace provides an extra
source of contact for these salts between the
fluid and solid phases. In fact, Clark (1965)
has suggested that the parathyroids are nonfunctional in this species.
No investigator has yet identified functional parathyroids in any of the fishes,
some of which do have bony skeletons
PARATHYROID PHYSIOLOGY IN MAMMALS
containing hydroxyapatite. However, the
physico-chemical relationship between these
more primitive bones and the circulating
fluids is also unknown. One might even
suggest that in these vertebrates the problem facing the animal may be the prevention of hypercalcemia instead of hypocalcemia, and that probably one should look
for thyrocalcitonin activity as preceding
that of parathyroid hormone in the evolutionary scheme.
Parathyroid Function: A Calcium Replacement Mechanism
The McLean feedback mechanism of
parathyroid action (McLean and Urist,
1955) visualized parathyroid hormone as
being released from the gland in response
to a drop in the level of ionized calcium in
the plasma circulating through it. In re-
827
sponse, this hormone acted on bone to
raise the level of calcium back to normal.
In 1962 we expanded this mechanism, postulating that the parathyroids function to
replace continuously the calcium lost from
plasma due to the concentration gradient
toward bone (Talmage, 1962), and presented a diagram of a model system describing our postulate. We are now presenting
a modification (Fig. 2) which has been corrected to include the possible role of thyrocalcitonin in the overall maintenance of
plasma calcium levels. The basic concepts
of the postulate remained unchanged, and
the reader is referred to the 1962 report for
details.
The above statements concerning the
need for parathyroid hormone are in accord
with our postulated model. Parathyroid
hormone is needed by the vertebrate whenever the physico-chemical relationships be-
CALCIUM REPLACEMENT MECHANISM
THYROIDS
PARATHYROIDS
KIDNEY
THRESHOLD
(NORMAL ANIMAL)
KIDNEY
THRESHOLD
(PTX ANIMAL)
PLASMA
FIG. 2. The diagrammatic presentation of the interrelationship of parathyroid hormone and thyro-
BONE
calcitonin in the maintenance of serum calcium
levels. Revised from Talmage (1962).
828
ROY V. TALMAGE
twecn bone and the circulating fluids are
such that a concentration gradient toward
bone exists, which must be the case if the
plasma calcium level is in the range of 10
mg/100 ml. The extent of the need for
parathyroid hormone would depend not
only on the slope of the concentration gradient curve, but also on the ease of contact
between the solid phase represented by
bone and the fluid phase represented by
blood and extracellular fluid. Therefore,
vascularization of bone and hemodynamic
considerations would be important factors.
The concentration of phosphate in the
plasma, which will be discussed in the next
section, would be another important factor.
At the present time these relationships are
easily demonstrable in the rat. In an earlier
report (Yoshida and Talmage, 1962), sufficient experimental evidence was collected
to allow the authors to postulate that a
similar replacement mechanism was operative in the bullfrog, Rana catesbeiana.
While work in this area with lower vertebrates has been minimal, the similarity between the frog and the rat encourages us
to postulate that the parathyroid glands
appeared phylogenetically when a calcium
replacement mechanism became necessary
to prevent levels of blood calcium from
falling below the physiological optimum.
It must be emphasized that, while the
basic equilibration level illustrated in Figure 2 is affected and possibly controlled primarily by physico-chemical considerations,
metabolic activity and therefore the involvement of bone cells is required. This
has been well demonstrated recently by the
dramatic effect of thyrocalcitonin in parathyroidectomized rats (Hirsch, 1967, and
Klein, et ah, 1967).
The Influence of Phosphate in Parathyroid
Physiology
Some years ago, parathyroid hormone was
considered to control the level of calcium
entirely through its ability to increase renal
excretion of phosphate. While parathyroid
hormone does increase the excretion of
phosphate, it does not control calcium levels
in this manner. It has been shown that the
hormone functions equally well in nephrectomized animals, and the plasma of vertebrates is not saturated with calcium and
phosphate as would be required by such
a theory of action (Albright and Reifenstein, 1948). However, phosphate has an
important influence on the rate of secretion
of parathyroid hormone and, therefore, on
the degree of participation of those glands
in the physiology of the animal. If an animal is placed on an extremely low phosphate diet containing normal or subnormal
calcium, the parathyroids become inactive
and often atrophy from disuse (Copp, et al.,
1965). On the other hand, if the phosphate
content of the plasma is elevated, either
experimentally by nephrectomy (Talmage,
et al., 1960), or by a high phosphate-tocalcium ratio in the diet, the gland becomes
overactive (Clark, 1967). In either case, the
calcium level of plasma may remain normal. This does not imply that the phosphate ion in any way directly controls the
rate of secretion of parathyroid hormone,
for this has been proven not to be the case
(Talmage and Toft, 1961). The influence
of phosphate must be explained by its effect
on the dynamics of calcium transport
through the blood and not on the calcium
level itself. In Figure 2, phosphate is indicated by the arrow to be acting on the normal gradient of movement of calcium from
the fluid to solid phase. If the amount of
phosphate is increased under constant concentrations of blood calcium, the rate of
deposition of calcium as well as phosphate
in bone is increased. This decreases the
ionic calcium concentration of the fluid
phase causing an immediate increase in
secretion of parathyroid hormone. If the
concentration of phosphate ions is decreased markedly, it is possible to reduce
the normal gradient of calcium movement
almost to zero and thereby negate the need
for parathyroid hormone. It is not surprising, then, that parathyroid activity can be
related to high phosphate-to-calcium ratios,
even if the total calcium in the diet is far
above normal (Clark, 1967).
It is unfortunate that in many studies of
parathyroid function, both in mammals
and in lower vertebrates, levels of phos-
PARATHYROID PHVSIOI.OCY IN MAMMALS
phate in plasma have been completely ignored. Indeed, if the plasma calcium is
controlled and maintained by parathyroid
secretion, it is the fluctuating phosphate
levels that actually control parathyroid activity. It must be emphasized that this concept is not connected in any way to the
effect of parathyroid hormone on renal
phosphate excretion which will be taken
up in the next section. It is of interest to
note that in many cases of normal increased
rates of bone growth, such as in the growing
child, the plasma phosphate levels are
elevated while the calcium levels remain
constant.
Extraosseous Effects of Parathyroid
Hormone
829
What is important is that the hormone
affects the transport of both calcium and
phosphate ions between blood and the
renal tubule, but in opposite directions
(Talmage and Kraintz, 1954). The hormone increases the tubular reabsorption of
calcium and decreases it for phosphate.
The net result of these reverse effects is to
permit the bone to economize on its release
of calcium, thereby conserving it for the
animal. (Note: There may still be investigators who believe the action of the hormone is on the secretion of phosphate by
the distal tubule. This concept has not yet
been disproven.) The sequence of action
appears to be as follows: Increased parathyroid secretion is produced by a drop in
the level of ionic calcium in plasma flowing
through the gland. The action of the hormone is to increase the release of both calcium and phosphate from bone. Simultaneously, additional phosphate is excreted
by the kidney, and more calcium is reabsorbed. The increased excretion of phosphate in many mammals, including man,
over-compensates for the additional release
of phosphate from bone, and, if continued,
may be effective in decreasing the concentration gradient for calcium and phosphate
toward bone. The increased rate for tubular reabsorption of calcium returns calcium
to the plasma and aids in raising plasma
calcium toward normal, reducing the
amount of calcium needed from bone. Cortelyou (1962) has presented data indicating
that a somewhat similar renal response to
parathyroid hormone occurs in the frog.
It is well recognized that the primary actions of parathyroid hormone are mediated
through bone cells. However, there are two
extraosseous sites where marked gradients
for calcium and/or phosphate ions occur,
and the influence of parathyroid hormone
has been implicated at both. One of these
is related to absorption of these ions from
the gut, and the other concerns their excretion through the kidney. We are not prepared to draw any conclusions concerning
stimulation of absorption of calcium in the
gut by parathyroid hormone. Reports can
be found supporting the concept of this
action of the hormone, including an earlier
one from our own laboratory (Talmage and
Elliott, 1958, and Cramer, et al, 1962).
Other reports either suggest a negative effect (Clark and Smith, 1964), namely increased absorption in the absence of the
parathyroid, or no effect (Wasserman and The Dual Role of Parathyroid Hormone in
Comar, 1961). Possibly there is an effect of Bone
the hormone here, but the variables effectUp to this point, we have been concerned
ing absorption in the gut are so numerous with the various metabolic activities surand so complex that the influence of the rounding the control of plasma levels of
hormone can not be clearly delineated. calcium and the rate of its transport
Whether or not there is an effect, it is through blood. Bone plays a major part in
hard to see how it could play an important this, as it is not only the cause of the conrole in the overall calcium homeostasis of centration gradient removing calcium from
the animal.
the fluid compartments, but also the source
While the effect of the hormone on the of calcium returned to fluid by the action
kidney may also be secondary to its role in of parathyroid hormone. Many studies
bone, it is nonetheless easily demonstrable. have demonstrated that the calcium sup-
830
ROY V. TALMACE
plied due to hormonal action is not that
which has been deposited recently (labile
bone) but, rather, that from older, deep,
stable bone (Talmage and Elliott, 1958b),
as indicated in Figure 2. One of the current
problems in parathyroid physiology is concerned with which cells respond to the hormone and what is the nature of their response. Two lines of research have been
emphasized: (1) In our laboratory (Talmage, 1967a), we have concentrated on
demonstrating the non-necessity of the osteoclast for the transfer of calcium from
bone to fluid under the influence of parathyroid hormone, and (2) others (Belanger,
et al., 1966) have demonstrated the influence of the hormone on the osteocyte. We
have emphasized that the hormone appears
to act directly on the mesenchyme or progenitor cell to form additional osteoclasts.
We have noted that the osteoclast is the
only bone cell which has not been proven
to have a cause-and-effect relationship to
parathyroid activity.
Therefore, we have recently postulated a
dual action of parathyroid hormone in bone
(Talmage, 1967b). The first action is
through individual cells, probably osteocytes, to increase the transfer of calcium
from bone to fluid. The second action is
through mesenchymal cells to increase the
rate of formation of osteoclasts, and thereby
the rate of bone remodelling. This suggests
that breakdown of bone by osteoclasts is
only an indirect result of parathyroid action
and plays only a passive role in providing
calcium for the maintenance of plasma
levels. If this postulate of dual action
proves to be correct, it is interesting to
speculate as to the phylogenetic importance
of each. Osteoclasts have been identified
in vertebrates as far down the scale as amphibians, but in frogs their numbers are
markedly reduced as compared to their
mammalian counterparts. Osteocytes, located in their lacunae, are relatively abundant. However, in our own earlier report,
we noted not only the existence of the replacement mechanism in the frog, but also
that endogenous parathyroid hormone increased the number of osteoclasts in the
shaft of the femur of this amphibian (Yoshida and Talmage, 1962).
The Relationship of Thyrocalcitonin to
Parathyroid Function
The recently discovered hypocalcemic
factor of the thyroid, thyrocalcitonin
(Hirsch, et al., 1964), has excited considerable interest among investigators interested
in calcium metabolism. We observed that
endogenous secretion could be demonstrated in the rat in the presence of high
calcium levels induced by intravenous infusion (Talmage, et al., 1965). Also, recent
studies (Care, 1967) have demonstrated the
presence of thyrocalcitonin in the blood of
several mammals following artificial production of hypercalcemia. This peptide
hormone (Munson, et al., 1966) is believed
to be secreted by the parafollicular cells of
the thyroid (Foster, et al., 1964) in the response to a rise in the ionic calcium, of
plasma above normal levels. Care (1967)
has suggested that the hormone may act as
a fine control of the plasma calcium level
working in opposition to parathyroid hormone whose function he relegates to that of
a coarse control.
Examination of the calcium replacement
mechanism pictured in Figure 2 suggests
that, according to our postulates, in those
animals having functional parathyroids and
an active concentration gradient for calcium toward bone, the problem facing the
animal is the prevention of hypocalcemia
and not hypercalcemia. Therefore, we can
not visualize an important role for this new
hormone in the physiology of the animal
if it is only secreted in response to hypercalcemia. Recently we have reported evidence, however, that endogenous secretion
occurs at normal, or even slightly subnormal, calcium levels in the rat (Klein and
Talmage, 1967). This evidence was based
on the suppression of removal of radioactive
calcium and phosphate, which had been
administered a week prior to a peritoneal
lavage procedure, in animals whose thyroids
were intact and functional but which were
hypocalcemic due to the removal of the
parathyroids. We concluded from this study
PARATHYROID PHYSIOLOGY IN MAMMALS
that this newly discovered hormone was
active in the normal animal and could,
therefore, play a part not only in the control of levels of calcium in the plasma but
also in remodelling processes of bone.
It seems clear from the results obtained
with thyrocalcitonin that a low rate of bone
resorption occurs continuously, unrelated
to parathyroid function. In Figure 2, this
is indicated as a contribution of "deep"
bone to the basic levels. Both that contribution induced by parathyroid hormone
and this resorption are suppressed by
thyrocalcitonin.
The role of thyrocalcitonin in lower vertebrates is yet unknown, though its existence has been demonstrated at least in birds
(Urist, 1967). Earlier in this report we suggested that, in vertebrate groups lower
phylogenetically than the amphibians, the
problems of hypercalcemia may be more
acute than those of hypocalcemia. Such a
condition could result from the fact that
the development of bone had not progressed to the point where a calcium concentration gradient toward bone existed.
These animals might, therefore, be subject
to surges in calcium absorption due to dietary conditions which could result in elevated levels of plasma calcium. For example, Urist (1963) has reported that the
calcium levels in the blood of some lower
vertebrates may run as high as 20 mg/100
ml. We will follow with interest any attempts that are made to establish the existence of thyrocalcitonin in these vertebrates.
The Problem of the Mechanism of Action
of Parathyroid Hormone
At the present time there is no agreement
among investigators as to which biochemical pathways are stimulated by parathyroid
hormone in producing its physiological
effects. It is our opinion that this is due
primarily to the difficulties of determining
the physico-chemical properties at the surface of bone and therefore the relationship
of cellular activity to the movement of calcium and phosphate in either direction.
The two most recent theories, that of organic acid production (Neuman, et al.,
831
1956) and mitochondrial transport (De
Luca, et al., 1962), have both been proven
inadequate or nonspecific. One of die problems that is still to be settled concerns the
concurrent dissolution of bone crystal and
the breakdown of the organic matrix upon
which it is deposited. As yet no experiment
has been devised which clearly demonstrates
that one component of bone is resorbed
first. Therefore, despite the fact that the
end result, physiologically, is the release of
calcium from bone, there are those (Belanger, et al., 1966) who are convinced that
enzymatic degradation of the organic matrix proceeds first, permitting the dissolution of bone crystals.
Every investigator has his favorite theory,
and ours is that the action of parathyroid
hormone and possibly even thyrocalcitonin
will be proven to be concerned with movement of calcium across cell membranes.
The major proponent of this is Borle
(1967), but unfortunately his test system,
the HeLa cells, is certainly not physiological. Briefly, his theory is that every cell has
a calcium pump, similar to the sodium
pump. Utilizing the expenditure of energy,
through systems not yet determined, intracellular calcium levels are kept minimal by
the active translocation of calcium to the
exterior of the cell. While there may be
metabolic agents which affect the rate of
the pumping action, Borle feels that parathyroid hormone acts on the cell membrane,
permitting a more active entry of calcium
into the cell. The stimulus to the pump
would result from increased intracellular
calcium.
There are major problems in explaining
the transport of calcium at sites in bone,
kidney, and gut by this mechanism. In
bone, the first problem is the delineation
of the types of bone cell directly affected
by the hormone. Enzymatic studies of homogenates of bone have of necessity been
carried out utilizing a variety of types of
bone cell with markedly different metabolic functions. It is not surprising that
many contradictory results have been obtained by such experiments. How much
progress can be expected in the next few
years is uncertain. However, now that the
832
Rov V. TALMAGE
knowledge o£ the physiology of thyrocalcitonin has almost caught up with that of
parathyroid hormone, a two-pronged attack can be made on the problem with a
better chance of success.
REFERENCES
Albright, F., and E. C. Reifenstein. 1948. The parathyroid glands and metabolic bone disease. The
Williams and Wilkins Company, Baltimore.
Belanger, L. F., T. Semba, S. Tolnai, D. H. Copp,
L. Kroom, and C. Gries. 1966. The two faces o£
resorption, p. 1-10. In H. Fleisch, H. J. J. Blackwood, and M. Owens, [ed.], Third European Symposium on Calcified Tissues. Springer-Veilag,
Berlin.
Borle, A. 1967. Personal communication.
Care, A. D. 1967. Measurement ot thyrocalcitonin
secretion rate by pig thyroid in vivo. Fed Proc.
26:367.
Clark, I. 1967. Personal communication.
Clark, I., and R. Smith. 1964. Effects o£ parathyroidectomy and hydrocortisone on the intestinal absorption o£ calcium and phosphate. Endocrinology 74:421-428.
Clark, N. B. 1965. Experimental and histological
studies o£ the parathyroid glands o£ fresh-water
turtles. Gen. Comp. Endocrinol. 5:297-303.
Copp, D. H., A. V. Kuczerpa, and L. F. Belanger.
1965. Effect of dietary Ca and P on plasma levels
and thyroid-parathyroid function in young rats.
Proc. Canad. Fed. Biol. Soc. 8:62.
Cortelyou, J. R. 1962. Phosphorus charges in totally
parathyroidectomized Rana pipiens. Endocrinology 70:618-624.
Cramer, C. F., A. P. Suider, and D. H. Copp. Parathyroid influence on calcium and phosphorus absorption by the gut, p. 158-166. In R. O. Greep
and R. V. Talmage, [ed.], The parathyroids.
Charles C Thomas, Springfield, 111.
DeLuca, H. F., G. W. Engstrom, and H. Rasmussen.
1962. The action of vitamin D and parathyroid
hormone in vitro on calcium uptake and release
by kidney mitochondria. Proc. Natl. Acad. Sci.
48:1604-09.
Foster, G.V., I. Maclntyre, and A. G. E. Pearse. 1964.
Calcitonin production in the mitochondrion-rich
cells of the dog thyroid. Nature 203:1029.
Hirsch, P. F. 1967. Thyrocalcitonin inhibition of
bone resorption induced by parathyroid extract
in thyroparathyroidectomized rats. Endocrinology
8:539-543.
Hirsch, P. F., E. F. Voelkel, and P. L. Miinson.
1964. Thyrocalcitonin: hypocalcemic hypophosphotemic principle of the thyroid gland. Science
146:142-143.
Klein, D. C., H. Morii, and R. V. Talmage. 1967.
Effect of thyrocalcitonin administered during
peritoneal lavage, on removal of bone salts and
their radioisotopes. Proc. Soc. Exptl. Biol. Med.
124:627-633.
Klein, D. C, and R. V. Talmage. 1968. Evidence
for secretion of thyrocalcitonin at normal and
subnormal plasma calcium levels. Endocrinology
82: (In press).
McLean, F. C, and M. R. Urist. 1955. Bone: An
introduction to the physiology of skeletal tissue.
University of Chicago Press, Chicago.
Munson, P. L., J. T. Potts, R. A. Reisfeld, C. W.
Cooper, and E. F. Voelkel. 1966. Further purification of pig thyrocalcitonin. Science 154:425.
Neuman, W. F., H. Firschein P. S. Chen, Jr., B. J.
Mulryan, and V. DiStefano. 1956. On the mechanism of action of parathormone. J. Am. Chem.
Soc. 78:3863-64.
Neuman, W. F., and M. W. Neuman. 1958. The
chemical dynamics of bone mineral. University of
Chicago Press, Chicago.
Talmage, R. V. 1962, Parathyroid function: a calcium replacement mechanism. Am. Zoologist 2:
353-360.
Talmage, R. V. 1967a. In Ann Budy, [ed.], Transactions of the Second Conference on Biology of Hard
Tissue. New York Academy o£ Science, New York,
II. (In press).
Talmage, R. V. 1967b. A study of the effect of
parathyroid hormone on bone remodeling and on
calcium homeostasis. Clin. Orthopaedics and Related Research. (In press.)
Talmage, R. V., and W. R. Hurst. 1950. Variability
in the response of symphysis pubis of the guinea
pig to relaxin. J. Endocrinol. 47:24-60.
Talmage, R. V., and J. R. Elliott. 1958a. Influence
o£ parathyroids on intestinal absorption o£ radiocalcium and radiostrontium. Federation Proc.
17:160.
Talmage, R. V., and J. R. Elliott. 19586. Effect of
time of injection on removal o£ Ca*5 and Sr85 by
peritoneal lavage. Proc. Soc. Exptl. Biol. Med. 99:
306-309.
Talmage, R. V., and F. W. Kraintz. 1954. Progressive changes in renal phosphate and calcium excretion in rats following parathyroidectomy or
parathyroid administration. Proc. Soc. Exptl. Biol.
Med. 87:263-267.
Talmage, R. V., J. Neuenschwander, and L. Kraintz.
1965. Evidence for thyrocalcitonin secretion in
the rat. Endocrinology 76:103.
Talmage, R. V., and R. J. Toft. 1961. The problem of the control of parathyroid secretion. In
R. O. Greep and R. V. Talmage, [ed.], The Parathyroids. Charles C Thomas, Springfield, 111.
Talmage, R. V., R. J. Toft, and R. Davis. 1960.
Clinical orthopaedics. No. 17, Chapt. 19. L. B.
Lippincott Co., Philadelphia, Pa.
Urist, M. R. 1963. The regulation of calcium and
other ions in the serum of hogfish and lampreys.
Ann. N.Y. Acad. Sci. 109:294-311.
Urist, M. R. 1967. Avian parathyroid physiology.
Am. Zoologist 7:883-895.
Wasserman, R. H., and C. L. Comar. 1961. The
parathyroids and the intestinal absorption of
PARATHVROII) PHVSIOI.OCV IN M A M M A L S
calcium, strontium and phosphate ions in the rat.
Endocrinology 69:1074-1079.
Yoshida, R., and R. V. Talmage. 1962. Removal of
833
calcium from Crog bone by peritoneal lavage; a
study of parathyroid function of amphibians.
Gen. Comp. Endocrinol. 2:551-557.