How’re they hangin’, guys?

While in the throes of working on my first investigational new drug (IND) application with its sketchy preclinical studies (and under a tight deadline), I happily distracted myself this evening with Jesse Bering’s Why do human testicles hang like that?

Granted, Gordon Gallup et al.’s research at face value seems anthropocentric as noted by a commenter, and evolutionary psychology is a highly speculative kind of science, but it’s an engaging article thanks to Bering’s (a columnist for Scientific American) sense of humor. A couple of my favorite passages pertaining to thermoregulatory properties of the ol’ nut sack and surrounding tissues:

It’s also why it’s generally inadvisable for men to wear tight-fitting jeans or especially snug “tighty whities”–under these restrictive conditions the testicles are shoved up against the body and artificially warmed so that the cremasteric muscle cannot do its job properly. Another reason not to wear these things is that it’s no longer 1988.

Like ambient heat generated by individual solar panels, when it comes to spermatic temperatures, the whole is greater than the sum of its parts. With a keen enough eye, presumably one could master the art of “ reading” testicle alignment, using the scrotum as a makeshift room thermometer . But that’s just me speculating.

I have to tip my crone’s beribboned red hat to men for their ability to poke fun at their nether parts as Dr. Bering and many male friends and colleagues do. I used to hear such jocularity frequently thanks to my research back in the day. Gather ’round, children, and I’ll tell you a tale.

Once upon a time, my work focused on enzymes involved with androgen biosynthesis: steroid 17alpha-hydroxylase/C17-20 lyase and steroid 5alpha-reductase.

Steroid 17alpha-hydroxylase/C17-20 lyase, also known as P450C17 or CYPc17, is a dual function enzyme that, depending on signaling from other enzymes that associate with it (these other enzymes feed CYPc17 electron equivalents), either makes glucocorticoids via the 17-hydroxylation activity or androgens which are in turn converted by other enzymes to testosterone or the estrogens.

Steroidogenesis for Dummies
Steroidogenesis for dummies

And here are the more detailed steps with structures:

CYPc17 and Lyase

The idea of the research was to come up with an inhibitor to act as a blockade of androgen production as a potential therapeutic for androgen-dependent prostate cancer. The bugaboo is that designing a selective inhibitor for this dual function enzyme is a tremendous hurdle, i.e., blocking C17-20 lyase activity without affecting 17-hydroxylase would be extremely difficult (one doesn’t want to fuck around with glucocorticoids in very ill patients).

Steroid 5alpha-reductase (5AR) converts testosterone to dihydrotestosterone (DHT) which binds even more tightly to the androgen receptor. DHT is a major player in conferring male-specific sex characteristics like facial and body hair growth, and deepening of the voice. It also contributes to male pattern baldness and benign prostatic hyperplasia (BPH). And in fact, there are 5AR inhibitors that are marketed drugs for BPH (Proscar) and male pattern baldness (Propecia). However, these drugs are teratogenic as all get out to a developing fetus. Not that a guy using these needs to worry, but his female partner who might become pregnant does.

Anyway, I worked on 5AR and P450c17 back in the day before recombinant DNA was routinely introduced into human cell culture to make recombinant proteins. Because these two enzymes are integral membrane proteins, they’re a bugger to isolate (they tend to curl up and die if pulled out of the membrane environment) so they must be studied in microsomal preps.

Back then in the Jurassic Era (early 90s), I had to gather human testicular and prostate tissue to isolate the membranes that held the enzymes. I was also the only female sr. scientist in the chemistry division at the time I studied these enzymes, and often the only woman present at group and project meetings. So invariably the fellows would make jokes about their testes and prostate and cover their crotches before we discussed my research. I didn’t find this offensive, but instead was amused. It’s like they had to get their concern about their ‘nads and their prostates out of the way first with sophomoric humor before we moved on to Serious Science.

At any rate, Bering’s humor reminded me of those good old days when I actually did science. Hence the fit of nostalgic reverie and my unending affection and amusement for the male of the species and their penchant for ball jokes.

13 thoughts on “How’re they hangin’, guys?”

  1. I loved this biochemistry and pharmacology review, and it took me back 15 years in addition to teaching me new stuff. But more to the point, I never wear underwear and I hope like crazy that I’m sterile. I hope to make all of these ends meet shortly.

    1. Thanks, Kev. I like Bering’s column and this one in particular tickled my fancy. Male plumbing is a fascinating thing.

  2. Your colleagues’ reaction to your research reminds me of anatomy lab. I was the only woman in a group of five students assigned to dissect a male cadaver. We called him ‘Clyde.’ We did all sorts of things to Clyde in the interests of pursuing anatomic knowledge – skinned various parts, de-fatted the axilla to look at the brachial plexus and the axillary artery and vein, took off the top of his skull and took out his brain, sawed his head in half so we could look at the sinuses – and then came the day to dissect his Clyde’s genitals. None of the guys would touch that particular dissection – it was all mine. One was brave enough to hold the legs apart for me and hand me instruments. The others stood at the opposite end of our tank, paging through the anatomy atlas, and occasionally wincing and asking ‘How could you?!’

    Oh, and another oddity of scrotal anatomy – scrotal contents connect through an opening called the processus vaginalis and through the inguinal canal with the preperitoneal space. So when I do a laparoscopic hernia repair, the scrotum ends up being inflated with carbon dioxide. It’ll go down on its own with time, but I had one attending in my fellowship who made me deflate the scrotum with a syringe and a needle prior to leaving the OR. AND the scrotum has an appalling tendency to bruise after hernia repair even if you haven’t touched it.

    Anway, this was a fun read this morning!

    1. “and then came the day to dissect his Clyde’s genitals. None of the guys would touch that particular dissection – it was all mine.”

      :^D That’s great!

      “So when I do a laparoscopic hernia repair, the scrotum ends up being inflated with carbon dioxide. ”

      Now that’s something I’d like to see! I have a wicked (and wholly inaccurate, I know) image of a puffed up scrotum flapping like a punctured balloon when pierced with a needle.

      1. It doesn’t flap, but it does deflate rather quickly. Heee, it’d be more fun if it flapped. :D

  3. “None of the guys would touch that particular dissection”

    I do recall from my gross anatomy days that I had no problem being the one in my foursome to make the first chest incision but discovering that when it came time to saw apart the guy’s bits, I wasn’t into it at all.

    It would be nice if there were a reliable linear relationship between scrotal laxity and temperature, as with the crickets-chirping thing. That way I wouldn’t have to load up to find out what it’s like outside, I could just assess my crotch. Unfortunately there are far too many confounding factors at work to make this practice at all feasible.

    1. could design a whole new set of icons to illustrate what the temperature translated into in terms of shrinkage. Temps in the 80s and above wold be “ballmy”, whereas anything below 30 could be something like “nuts to you”.

      1. Then there’s the whole issue of traditional (penile) shrinkage operating independently of scrotal shrinkage. The whole cold-water thing doesn’t get anywhere close to the heart of the matter. These poor women researchers (even skilled surgeons!) will never elucidate the details, try as they might.

  4. “That way I wouldn’t have to load up to find out what it’s like outside, I could just assess my crotch. ”

    Yeah, but like those home weather systems, it would only work if you have a “remote crotch” to supplement the standard base station crotch.

  5. Right across the hall from our electrical labs are a bunch of bio labs. A few years ago when they put in a new cadaver lab, I took a tour with some of the other staff. One of the cadavers had seen some major work including having his penis cut though 90% about halfway down. It just sort of hanging tenuously. It didn’t bother me a bit. No, what bothered me, as a runner no doubt, was seeing a lower leg that had been stripped of all skin with the Achilles tendon completely severed. A completely severed Achilles! I could almost feel that. The penis slicing, eh, not so much.

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