Charles McCormack

Charles McCormack

It is a great honor to be invited by the American Physiological Society to participate in their “Living History” Program. Like anyone else who has gained commendation, I have many to thank. In fact, any success I might claim is totally dependent upon being influenced by the right person at the right time. In this narrative, I shall mention many who have helped me, but shall probably fail to mention many more. Let me begin with a brief portrayal of my early childhood, which, of course, formed the framework for my curiosity that led me to a career in science.

Childhood years

I was born in 1938 in rural northern Illinois as the third of six children in a farm family.  When I was three years old we moved 20 miles north to rural southern Wisconsin. 1944, I remember being the only first grader in a rural one-room school of 13 students - my older sister, older brother and I being 3 of the 13.  Our kind enthusiastic teacher (Miss Braun), who taught all eight grades, managed to maintain a pleasant atmosphere in her lively classroom.  Because I was able to complete my assignments rather quickly, I could spend most of the day listening to the interesting classes of older students.  My later experiences in somewhat larger grade schools were similarly stimulating - every teacher was noteworthy in one or more ways.  My older brother and sister were “live-in tutors” for me, assisting me on anything from arithmetic to getting along with my classmates.  I credit my father for first stimulating my interest in reproductive endocrinology as he always kept us involved in the rearing of our farm animals.  Observing animals breeding, giving birth, and nursing was truly fascinating.  Also, my brother and I helped my father castrate weanling male pigs. (Dad said it would keep them from fighting each other.) I realize now that my farm-background was better training for my career in physiology than the most esteemed city school.  I should also mention that my parents, along with the local Methodist Church, were very open-minded, and never hindered my curiosity.

High School and College years

Sometime during high school, I decided that I could best continue my study of biology and chemistry by becoming a medical doctor.  My parents thought that I would perform better in a small liberal arts college than at a larger college or university.   So it was, that one Saturday in April, a recruiter, Ms. Shirley Hilger, from Carroll College (650 students in Waukesha Wisconsin) was at our kitchen table.  She, my parents, and I quickly filled out two pages of forms, and I wrote a brief paragraph describing my ambitions.  A couple of weeks later, I received a letter notifying me that I had been admitted to Carroll, and also that Carroll was awarding me a scholarship to cover half of my tuition, room and board.  The additional expense for my entire freshman year would only be $600.  This, I met through summer employment at a local mink ranch (which provided good practice for handling much more docile lab-rats), and part time work during the school year - initially as a janitor, and later as a biology-teaching assistant.  I also acquired an interest-free loan for $600 from the Methodist Church.  (Contrast these low costs to what college students must pay today.)  Besides studying chemistry and biology, wrestling, as a 130 “pounder”, filled my time.  Incidentally, being on the wrestling team forced me to stay in physical condition, and to develop good eating habits and exercise routines.  I suspect this accounts for some of the good health I still enjoy today.

Graduate School years

Midway during my senior year at Carroll College, I noticed on a bulletin board, graduate-school fliers describing teaching assistantships at universities.  These   assistantships paid a stipend of about $200/month (enough to live on), and a full tuition waiver.  I hastened to ask my biology professor, Dr. Roy Christoph, what a graduate education in biology entailed?  He answered: “You do research in biology, earn a PhD, and then make your living as a researcher, or as a teacher like me.”   Within a matter of days, my desire to go to medical school waned; it seems that biological research was my actual interest.  Earlier in the year, I had completed a fascinating course in endocrinology taught by Dr. Christoph, so I asked him if any professor in the University of Wisconsin, Zoology Department was doing endocrine research.  He referred me to Roland K. Meyer, PhD, a well-recognized endocrinologist. I wrote to Dr. Meyer, who quickly wrote back, inviting me for an interview regarding the possibility of working with him as a research fellow in a new Endocrinology-Training-Program at the university.  I soon made the 60-mile trip to Madison, talked to Dr. Meyer for about a half hour; whereupon he offered me a Wisconsin Alumni Research Foundation Fellowship (WARF) to study under him.  As a result, in mid June of 1959, two weeks after graduating from Carroll, I started graduate school.  Most importantly, a WARF Fellowship, did not require me to teach; therefore, I could begin a research project immediately.  That is exactly what Dr. Meyer had me do!   

Dr. Meyer wanted me to develop an assay for the release of endogenous luteinizing hormone (LH) using the induction of ovulation in weaning female rats as the endpoint.  We would prime the ovaries of 22 day-old rats by injection of pregnant mare’s serum gonadotropin PMSG (an inexpensive source of follicle stimulating hormone [FSH]), and then, two days later inject extracts of porcine hypothalamic median eminence tissue intravenously (iv).  Presumably, if hypothalamic LH-releasing factor were present in the extract, it would elicit a surge of endogenous LH, which, in turn, would elicit ovulation1.  About a decade earlier, experimental studies by Dr. Geoffrey Harris (see Harris 1972 for references) had demonstrated that some “factor” from the hypothalamus (“LHRF”) had to be released into the hypothalamo-hypophyseal portal vessels for ovulation to occur in rabbits, rats and presumably in women.  If an LH surge was elicited in our weanling rats, we expected them to ovulate.  Our evidence of ovulation would be the presence of freshly ovulated ova in the oviducts on the morning following the i.v. injections.  Positive controls injected with human chorionic gonadotropin (hCG = LH) ovulated, negative controls injected with the hormone-vehicle (isotonic saline) did not, but neither did rats injected with extracts from porcine median eminence. (I had collected porcine median eminence tissue from the local meat processor, Oscar Mayer.)  Seeing these negative results, Dr. Meyer suggested that I sensitize the weanling rats to the median eminence extracts by pretreating the rats with exogenous estrogen, because estrogen had long been considered to be the hormonal signal that triggered the LH-surge that caused ovulation (Fevold et al, 1936).  The addition of estrogen to our priming regimen caused about 20 % of the rats to ovulate, but injecting porcine median eminence extracts did not further increase the percentage of rats ovulating.

Around this time, I read an article by John Everett and Charles Sawyer (1949) working at Duke University demonstrating that injecting progesterone on the second day of diestrus in adult female rats advanced the time of ovulation by an entire day.  This suggested to me that administering progesterone might sensitize our assay rats to the LHRH that presumably was present in the median eminence extracts.   To my surprise, giving progesterone caused all of our rats to ovulate whether they were given median eminence extract or the extract-vehicle, isotonic saline.  To determine whether progesterone was eliciting an ovulation-inducing surge of LH, we administered progesterone at 10 AM and then removed the pituitary gland four hours later, i.e., at 2 PM.  Ovulation did not occur.  But if we delayed removal of the pituitary until 5 PM, the rats ovulated.  Earlier, Everett and Sawyer had demonstrated that the ovulation-inducing surge of LH occurred in adult rats during this same 2-5 PM interval, which they referred to as the “critical period” for LH-secretion.  So, although I had not succeeded in sensitizing our assay rats to exogenous LHRH, I had shown that progesterone was a potent facilitator of LH-secretion in PMSG-primed weanling rats.  Fortunately, Dr. Meyer considered this to be an important finding; therefore he allowed me to drop our search for LHRF, and instead concentrate on progesterone-facilitation of LH-secretion.

During the next two years, I demonstrated 1) that doses of progesterone that are less than 1/10th the dose necessary to inhibit LH-secretion would elicit LH-secretion and ovulation; 2) that progesterone induced ovulation if injected prior to (but not after) the “critical period for LH secretion”; 3) that progesterone could elicit LH-secretion (ovulation) in rats as young as 18 days of age; 4) that only progesterone and progesterone-analogs (medroxyprogesterone, norethynodrel) elicited ovulation; whereas estradiol, estrone, and testosterone did not.  These findings allowed me to defend my PhD thesis successfully four years after I arrived in Madison (McCormack C.E. 1963).  More importantly, my findings caught the attention of several reproductive endocrinologists; thereby allowing me in future years to share ideas with leaders in the field of neuroendocrinology - to name just a few: Lester E. Casida, William McShan, Neena B. Schwartz2, John Everett, Charles Sawyer, J.T. Bradbury, Charles Barraclough, S.M. McCann, Domingo Ramirez, M.X. Zarrow, Al Parlow, William F. Ganong, Andrew Nalbandov, and Ernst Knobil.

My research-years at The Chicago Medical School (CMS)

After only one year of postdoctoral study at Madison, I decided to look for an academic position. This task was made easier, because the “birth control pill” had just come out, and those of us with training in reproductive physiology looked interesting to the pharmaceutical industry and academic institutions. The most interesting offer came from the Department of Physiology and Biophysics at The Chicago Medical School (CMS).  I would only be required to give about ten lectures each year, and help supervise in the medical student “dog labs” labs one afternoon each week for half the year.  Thus, in September of 1964, I took an  “Instructorship” at CMS, but with no intention of doing a lot of instruction.  Paradoxically, I ended up doing a great deal of instruction at CMS, and am still doing so 53 years later.

Let me backtrack to Madison for a bit.  While still there, a fellow graduate student, William (Bill) F. Strauss and I served as one another’s sounding boards for experimental design.  In a superbly designed experiment, Bill showed that the time of the critical period for LH-secretion in pre-pubertal rats could be modified with a single light signal made a week prior to administering the PMSG. What Bill did was to begin continuous darkness (DD) either five-hours earlier than the standard time of “lights off”, or five-hours later than the standard time of “lights off.   Amazingly, in response to this one last “lights off” signal, the “critical period” of LH secretion shifted earlier if DD started 5 hours earlier, and shifted later if DD started 5 hours later (Strauss W.F. 1964). This indicated that the rhythm controlling LH-secretion had the characteristics on an endogenous circadian rhythm (Aschoff J.,1960).  This finding intrigued me so much that I spent my first 25 years at CMS exploring the circadian characteristics of the LH rhythm.  During these years, my graduate students and I demonstrated that the LH rhythm was truly circadian (i.e. obeyed Aschoff’s rules) in PMSG-primed immature rats and in adult rats.  Furthermore, we demonstrated that the periodicity (free-running period”) of the LH rhythm was identical in duration to the rhythm of spontaneous locomotion (McCormack & Bennin, 1970, Sridaran & McCormack, 1980).  During these years, I mentored three PhD students3 in reproductive endocrinology, all three of which are currently professors in academic departments of medical schools.  While proud of research we conducted at CMS, I realize now that I should have also continued investigating the role of progesterone in eliciting the ovulation-inducing surge of LH-secretion.  Indeed, in the last 35 years, others have shown that progesterone is an important (perhaps the most important) steroidal signal triggering the ovulation-inducing LH surge in women (Hoff,J.D. et al 1983). 

My teaching-years at CMS

In 1988, a new Chair of our department, Dr. Richard Hawkins, asked me to become the director of our medical physiology course.   As I no longer had extramural research funding, I felt that I should accept the assignment.  You will remember that teaching was not my reason for coming to CMS, but four things had since caused me to embrace teaching.  First, for my first 40 years at CMS, our department required that our medical students perform classic “dog labs”.  Not having been previously trained in large animal surgical procedures, I am very grateful that in the mid 1960’s a highly skillful professor in our department, (Jay Smith, PhD) took the necessary time to teach me the surgical skills and basic physiology essential for conducting dog-labs.  Having to participate in all the dog-labs forced me to learn classical systemic physiology (cardiovascular, respiratory, gastrointestinal, and renal physiology).  Second, whenever our department lost a lecturer for any physiological system, I was assigned the task.  Thus, I learned to give the complete lecture-series in gastrointestinal, respiratory, endocrine, reproductive, and renal physiology.  Third, I am especially grateful for another former Chair (Robert Rakowski - now deceased) for insisting that I understand fundamental aspects of membrane-physiology.  This knowledge has enabled me to develop a deeper understanding of all areas of systemic physiology.  Fourth, in the early 1990’s, I taught (moon-lighted) for a USMLE review-company, and thus had to give lectures for all the physiology-systems.  So, by circumstance, more so than by design, I became a fairly knowledgeable systemic physiologist.  As a result, over the past twenty years, I have taught second-year-medial school elective-courses in cardiovascular pathophysiology and respiratory pathophysiology, as well as in reproductive endocrinology.

Three years ago, after 25 years of directing our medicaI physiology course, I willingly gave up the directorship and simultaneously went to “half-time” employment4.  However, I still direct our department’s ten teaching assistants who help the M-1 students solve problems in all areas of medical physiology.  This, as well as continuing to offer my elective courses, keeps me on campus much more than half time.  But then, it has taken me most of my life to become a reasonably competent systemic physiologist, so it seems ridiculous to give this up for more time at home and/or traveling.  Yes, as you have probably already surmised, I owe the most gratitude of all to my wife, Claire, of 55 years (we met as students at Carroll College), who has given up much time during her “golden years” to allow me to continue pursuing physiology - my “other” passion”.

I also would like to thank the American Physiological Society.  Executive Secretary, Marty Frank PhD, has been a strong supporter of our entire department for many years.  My only non-endocrine, graduate student, Ms. Darlene Racker PhD, was one of the first APS Porter Foundation Fellows.  Darlene actively investigated the conductile-system of the heart here at CMS and at Northwestern University until her retirement a couple of years ago.  Finally, as I write this narrative, I look forward to attending the “course-director’s meeting” at the annual meeting of APS, even though I am no longer a course-director.

Kindest regards to all my colleagues at APS,



1         Keep in mind that we were attempting to develop this ovulation-assay to years before S.M.McCann demonstrated that extracts from the hypothalamus would elicit LH-secretion as evidenced by ovarian ascorbic acid depletion in a different assay also utilizing immature rats.

2     More than anyone else, Neena Schwartz PhD, who in 1964 was already performing classic steroid-feedback studies at the University of Illinois Medical School located just 4 blocks from CMS.  Neena became my trusted friend, mentor, and colleague upon my arrival to Chicago.

3     My three PhD students in reproductive endocrinology were Rajagapola

Sridaran, (Moorehouse College of Medicine), Phyllis Cheung Zee, Northwestern University, College of Medcine), James Ferraro (Southern Illinois Univ., School of Medicine).

4     I thank my current Chair, Janice Urban, PhD for allowing me to go half time, and yet retain my tenure.

5      Although, given the name, Charles, at my birth in 1938, I was a fourth generation Charles McCormack (the first three generations still being alive); thus I was immediately tagged with the nickname, Pat.


Aschoff, J (1960) Exogenous and endogenous components in circadian rhythms. Cold Spring Harbor Symp Qunat Biol 25:11-27.

Everett, J.W. & Sawyer, C.H. (1949) A neural timing factor in the mechanism by which progesterone advances ovulation in the cyclic rat. Endocrinology 45: 585-595.

Fevold, H. L., Hisaw, F.L., & Greep, R (1936) Effect of oestrin on the activity of the anterior lobe of the pituitary.  Am J Physiol. 114:508-513.

Harris, G.W. (1972) Humours and Hormones. The Sir Henry Dale Lecture for 19781. Journal of Endocrinology 53:1-23

Hoff,J.D., Quigley, M.E., Yen, S.S.C. (1983) Hormonal dynamics at midcycle: A reevaluation. J. Clin. Endo. Metab. 57:792-796.

McCann, S.M. (1962) A hypothalamic luteinizing hormone releasing factor.  American J. of Physiology 202:395-400.

McCormack,C.E. (1963) The control of ovulating hormone release in immature rats. PhD Thesis University of Wisconsin, Madison, Library

McCormack, C.E. & Meyer, R.K. (1963) Ovulation induced by progesterone in immature rats pretreated with pregnant mare serum gonadotropin. General and Comparative Endocrinology 3:300-307

McCormack C.E. & Bennin, B (1970) Delay of ovulation caused by exposure to continuous light in immature rats treated with Pregnant Mare’s Serum Gonadotropin, Endocrinology 86:611-619

Odell, W.D. and Swerdloff, R.S. (1968) Progestogen-induced luteinizing and follicle-stimulating hormone surge in postmenopausal women:  A simulated ovulatory peak.  Proc. Nat Acad Sci 61: 529-536.

Sridaran, R & McCormack, C.E. (1980) Parallel effects of light signals on the circadian rhythms of running activity and ovulation in rats.  J. Endocrinology 85: 111-120.

Strauss, W.F. (1964) Neural timing of ovulation in immature rats treated with gonadotropin.  PhD Thesis University of Wisconsin, Madison, Library.