INSL3
The insulin-family hormone behind testicular descent, and why its steady blood level is studied as a gauge of the testis
INSL3, insulin-like peptide 3, is a two-chain hormone made by Leydig cells in the testis and theca cells in the ovary. Before birth it builds the ligament that brings the testes down into the scrotum. In adult men its level reflects how many working Leydig cells there are, falls with age about eight times faster than testosterone, and hardly varies from day to day, which is why it is studied as a marker. In women it tracks growing follicles. It has never been given to people.
No established human dose Details ↓
Recommended Dosing
No established human dose
INSL3 has not been given to people in any study on this page. Every human study measured it, in cord blood, in serum across life, in men whose testes were suppressed by other drugs or stimulated with hCG, and in women across the cycle.
What is it?
INSL3 is a hormone of the insulin and relaxin family, built like insulin from two short chains held together by disulfide bonds. It goes by several names from its history: Leydig insulin-like peptide, relaxin-like factor, insulin-like factor 3. In men it comes from the Leydig cells, the same testicular cells that make testosterone; in women from the theca cells that wrap growing ovarian follicles.
Its best-understood job happens before birth. The testes form high in the abdomen and must move down, guided by a cord of tissue called the gubernaculum. INSL3 makes that cord grow. Mice bred without INSL3, or without its receptor RXFP2, keep their testes in the abdomen. In boys, lower INSL3 in cord blood has been linked with undescended testes, although mutations in the gene itself turn out to be a rare cause.
In adult men INSL3 behaves unlike testosterone. Testosterone swings with the pituitary's LH pulses, the time of day and illness, and the pituitary pushes harder as the testes age, which props testosterone up. INSL3 is released at a steady rate set by how many mature Leydig cells there are. In a large European cohort it fell about 15% per decade from age 40, while testosterone fell about 2%, and men with low levels when young tended to stay low. It drops when the testes are switched off by testosterone injections, a GnRH agonist or castration, and it is almost absent in men born without pituitary drive to the testes until hCG is given.
Those properties are why researchers propose INSL3 as a gauge of testicular reserve that a single testosterone test can miss. In older men it predicted several age-related illnesses about four years ahead as well as free testosterone did, and its link with lower bone density survived adjustment for other factors, which has kept interest in a role for INSL3 in bone. In women its level rises and falls with follicle growth, is higher in polycystic ovary syndrome and is lower in premature ovarian insufficiency.
None of this has produced a treatment. INSL3 has not been given to people in any study read, and its use as a clinical test is still being defined; most work on what it does in the body comes from animals.
Mechanism of Action
INSL3 acts on one receptor, RXFP2. Before birth that builds the gubernaculum that brings the testes down; in adults its steady secretion mirrors Leydig and theca cell capacity.
Testicular descent
INSL3 makes the gubernaculum grow in the fetus, without needing androgens; mice lacking it keep both testes in the abdomen.
RXFP2 receptor
It binds RXFP2 (LGR8), a G protein-coupled receptor, and raises cAMP in the cells that carry it.
A gauge of Leydig cells
Adult Leydig cells release INSL3 steadily according to their number and maturity, so its level changes slowly, unlike testosterone.
Follicle growth
In women theca cells of growing follicles secrete it, and it supports the androgen supply that granulosa cells turn into oestrogen.
Published Research
These are studies of INSL3 and its gene, read from their PubMed abstracts: the mouse knockouts and receptor study that showed what it does, genetic and cord-blood studies in boys with undescended testes, cohort and clinical studies of INSL3 in men and women, a study of testicular suppression, and two reviews. INSL3 is measured in every human study here; none gave it.
No INSL3, no testicular descent
Male mice with the Insl3 gene deleted had both testes left high in the abdomen because the gubernaculum, the ligament that guides the testis down, never developed. Mice lacking both Insl3 and the androgen receptor showed that INSL3 builds the gubernaculum without androgens, while androgens separately remove the ligament that holds the gonad up.
Infertile males and subfertile females
A second Insl3 knockout line confirmed bilateral undescended testes from a gubernaculum defect, leading to faulty sperm production and infertility. Female mice without Insl3 also had reduced fertility with a disturbed oestrous cycle.
INSL3 is the hormone for LGR8
INSL3 raised cAMP in cells carrying the orphan receptor LGR8 but not the related LGR7, and cross-linking showed the two bind. LGR8 was expressed in the gubernaculum, and INSL3 stimulated cAMP and cell division in cultured gubernacular cells. The receptor is now called RXFP2.
Gene changes are rare in familial cryptorchidism
Sequencing INSL3 and its receptor gene in 13 men with personal and family histories of undescended testes found only known variants, and the receptor variant tested worked normally. The authors concluded that mutations in these genes explain only a small share of familial cryptorchidism.
INSL3 falls with age in 1,183 men
In a random sample of South Australian men, serum INSL3 fell steadily from about 1.29 ng/mL at 35 to 44 years to about 0.79 ng/mL at 75 to 80 years. It did not track testosterone or the pituitary hormones once age was allowed for, and men with one testis removed sat between intact and anorchid men, consistent with INSL3 measuring Leydig cell number and quality.
Higher INSL3 when hormonal contraception leaves sperm
In 107 men from three male hormonal contraceptive studies, baseline INSL3 did not predict who became azoospermic, but at the end of treatment men who still had sperm had higher serum INSL3, and INSL3 correlated with sperm concentration. The authors suggested INSL3 may help some sperm production survive gonadotropin suppression.
High in newborn boys, absent in girls
INSL3 was much higher in cord blood and at three months than in older boys, tracked LH in three-month-old boys, and was unmeasurable in girls at every age. Boys whose testes stayed undescended had lower cord blood INSL3 and a higher LH to INSL3 ratio at three months, pointing to weaker Leydig cell function around birth.
INSL3 across the menstrual cycle
In 18 healthy women sampled every two to three days, INSL3 rose and fell with the growth of antral follicles in both halves of the cycle and was higher than during menstruation. Among 909 women at an infertility clinic, those with polycystic ovary syndrome had higher INSL3 and those with low ovarian reserve had lower levels.
INSL3 and AMH rise together in PCOS
In 57 women with polycystic ovary syndrome and 27 controls, INSL3 was higher in those with absent or infrequent periods than in controls, and INSL3 correlated with anti-Mullerian hormone. The authors read INSL3 as a marker of the theca cell side of the syndrome.
Low in Klinefelter syndrome, not in osteoporosis
Plasma INSL3 was about half the control level in four men with Klinefelter syndrome, reflecting testicular failure, but men with osteoporosis as a group did not have lower INSL3 than healthy men; the small primary osteoporosis subgroup actually had higher levels.
Near zero in untreated hypogonadotropic men
In 281 men with congenital hypogonadotropic hypogonadism or Kallmann syndrome, untreated patients averaged about 60 pg/mL against about 659 pg/mL in 72 healthy men, with no overlap at a 250 pg/mL threshold. Testosterone treatment left INSL3 low, while hCG with FSH, or hCG alone, raised it, showing that adult INSL3 depends on LH-type stimulation of the Leydig cells.
Lower cord blood INSL3 in undescended testis
In a case-control study of 180 boys born after 34 weeks, cord blood INSL3 was lower in the 52 boys with undescended testes, especially when the condition resolved on its own and when the testis could not be felt, while testosterone and the other hormones measured did not differ.
Falling INSL3 as ovarian reserve runs out
In 145 women, serum INSL3 fell step by step from normal ovarian reserve to biochemical and then overt premature ovarian insufficiency. It correlated negatively with FSH and positively with anti-Mullerian hormone, inhibin B and antral follicle count, and it predicted insufficiency well; follicular fluid levels did not differ.
About 15% lower per decade in European men
In the European Male Aging Study, INSL3 fell about 15% per decade from age 40 both across men and within the same men over time, against about 1.9% per decade for testosterone. It was lower with higher body mass index, waist size and smoking, did not rise with weight loss as testosterone does, and gave an age-adjusted European reference range.
INSL3 and later illness in older men
In the same cohort, unadjusted INSL3 tracked hypogonadism and was linked with lower sexual function, bone density and activity and with more hypertension, heart disease, cancer and diabetes. After adjustment only lower bone density stayed linked, but INSL3 measured at the first visit predicted seven of nine illness groups about 4.3 years later, as well as calculated free testosterone did.
INSL3 drops when the testes are switched off
INSL3, testosterone and LH all fell when testicular function was suppressed in three settings: healthy young men given testosterone injections, transgender girls on a GnRH agonist, and men with prostate cancer randomised to castration or a GnRH agonist. In the healthy men all three recovered after suppression ended. The authors suggested INSL3 could help detect illicit androgen use.
A marker of Leydig cell function
This review describes INSL3 as secreted constantly by Leydig cells according to their number and maturity rather than in acute response to LH, which makes it more sensitive than testosterone to Leydig cell damage. It also covers proposed effects on bone and muscle and argues that low INSL3 may contribute to sarcopenia and osteoporosis in hypogonadal men.
INSL3 in female reproduction
This review describes INSL3 made by theca cells of growing follicles, acting through RXFP2 to drive the androstenedione that granulosa cells turn into oestrogen. Its blood level follows follicle growth, rises in polycystic ovary syndrome and falls in premature ovarian failure, and the authors note that most of the evidence still comes from animals.
No Established Human Dose
INSL3 has not been given to people in any study on this page. Every human study measured it, in cord blood, in serum across life, in men whose testes were suppressed by other drugs or stimulated with hCG, and in women across the cycle. There is no INSL3 product and no dose to state.
What this rests on: PMID 35770372, PMID 24243640, PMID 37235781.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes INSL3 is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of INSL3 has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store INSL3, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long INSL3 stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking INSL3. What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
Unknown: no cited half-life and no label or trial duration on this page says how long INSL3 lasts or how long it was given. Results reported in the studies are under Published Research.
Side effects, and when to stop or get help
From the Side Effects section: No study here administered INSL3, so nothing is known about its effects when given to people; Its level is lowered by testosterone injections and GnRH agonists, which can mask a testicular problem or reveal suppression (PMID 37235781); Body weight and smoking are linked with lower INSL3 in men, which affects how a single value is read (PMID 35770372). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping INSL3. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“INSL3 is measured, not given, so it has no side effects of its own”).
Interactions
Unknown: a PubMed search for human interaction studies of INSL3 (reviewed 2026-10-30) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of INSL3 products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against INSL3's expected mass, 6,630.7 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a medicine: INSL3 is measured in blood by immunoassay or mass spectrometry and has not been given to people as a drug). Sport: Not on the 2026 List.
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
INSL3 is measured, not given, so it has no side effects of its own.
Contraindications & Cautions
There is no INSL3 medicine. These cautions concern reading the test.
Legal Status
INSL3 is a hormone measured in blood; it is not approved as a medicine anywhere in the sources read.
Frequently Asked Questions
?What is INSL3?
Insulin-like peptide 3, a two-chain hormone related to insulin and relaxin. Men make it in the Leydig cells of the testes and women in the theca cells of growing ovarian follicles.
?What does INSL3 do?
Before birth it grows the gubernaculum, the ligament that brings the testes down into the scrotum. In adults its roles are less settled; it is studied in sperm production, in follicle development and, in men, in bone.
?Why measure INSL3 instead of testosterone?
Because it is steadier. Testosterone shifts with the time of day, illness and the pituitary's push, while INSL3 reflects how many working Leydig cells there are. In older men it fell about eight times faster than testosterone per decade.
?Is low INSL3 linked to undescended testes?
Cord-blood INSL3 was lower in boys with undescended testes in two studies, while testosterone did not differ. Mutations in the INSL3 gene itself are a rare cause.
?Does testosterone therapy affect INSL3?
Yes. Testosterone injections lowered INSL3 along with LH in healthy men, and it recovered after they stopped; in men lacking pituitary drive, testosterone left INSL3 low while hCG raised it.
?What does INSL3 show in women?
It rises with growing antral follicles across the cycle, is higher in polycystic ovary syndrome and is lower as ovarian reserve runs out, so it is being studied as a theca cell marker.
?Can you take INSL3?
No. It has never been given to people in the studies read and no INSL3 product exists.
References
- [other] UniProt P51460 (INSL3_HUMAN), B chain = residues 21-55, A chain = residues 106-131, two interchain and one intrachain disulfide bond; read October 30, 2026. Formula and mass computed from the two chains with three disulfides. https://www.uniprot.org/uniprotkb/P51460/entry
- [pubmed] Zimmermann S, et al. "Targeted disruption of the Insl3 gene causes bilateral cryptorchidism." Mol Endocrinol, 1999;13(5):681-91. PMID: 10319319.
- [pubmed] Nef S, et al. "Cryptorchidism in mice mutant for Insl3." Nat Genet, 1999;22(3):295-9. PMID: 10391220.
- [pubmed] Kumagai J, et al. "INSL3/Leydig insulin-like peptide activates the LGR8 receptor important in testis descent." J Biol Chem, 2002;277(35):31283-6. PMID: 12114498.
- [pubmed] Feng S, et al. "Mutation analysis of INSL3 and GREAT/LGR8 genes in familial cryptorchidism." Urology, 2004;64(5):1032-6. PMID: 15533513.
- [pubmed] Anand-Ivell R, et al. "Peripheral INSL3 concentrations decline with age in a large population of Australian men." Int J Androl, 2006;29(6):618-26. PMID: 17014531.
- [pubmed] Amory JK, et al. "Elevated end-of-treatment serum INSL3 is associated with failure to completely suppress spermatogenesis in men receiving male hormonal contraception." J Androl, 2007;28(4):548-54. PMID: 17314233.
- [pubmed] Bay K, et al. "Insulin-like factor 3 levels in cord blood and serum from children: effects of age, postnatal hypothalamic-pituitary-gonadal axis activation, and cryptorchidism." J Clin Endocrinol Metab, 2007;92(10):4020-7. PMID: 17666478.
- [pubmed] Anand-Ivell R, et al. "Circulating insulin-like factor 3 (INSL3) in healthy and infertile women." Hum Reprod, 2013;28(11):3093-102. PMID: 24014601.
- [pubmed] Pelusi C, et al. "Parallel variations of insulin-like peptide 3 (INSL3) and antimüllerian hormone (AMH) in women with the polycystic ovary syndrome according to menstrual cycle pattern." J Clin Endocrinol Metab, 2013;98(10):E1575-82. PMID: 23928669.
- [pubmed] Hussain A, et al. "Plasma insulin-like factor 3 (INSL3) in male patients with osteoporosis and Klinefelter's syndrome." Ital J Anat Embryol, 2013;118(1 Suppl):34-6. PMID: 24640568.
- [pubmed] Trabado S, et al. "Insulin-like peptide 3 (INSL3) in men with congenital hypogonadotropic hypogonadism/Kallmann syndrome and effects of different modalities of hormonal treatment: a single-center study of 281 patients." J Clin Endocrinol Metab, 2014;99(2):E268-75. PMID: 24243640.
- [pubmed] Fénichel P, et al. "Cord blood insulin-like peptide 3 (INSL3) but not testosterone is reduced in idiopathic cryptorchidism." Clin Endocrinol (Oxf), 2015;82(2):242-7. PMID: 24826892.
- [pubmed] Zhu C, et al. "New theca-cell marker insulin-like factor 3 is associated with premature ovarian insufficiency." Fertil Steril, 2021;115(2):455-462. PMID: 33041054.
- [pubmed] Anand-Ivell R, et al. "Association of age, hormonal, and lifestyle factors with the Leydig cell biomarker INSL3 in aging men from the European Male Aging Study cohort." Andrology, 2022;10(7):1328-1338. PMID: 35770372.
- [pubmed] Ivell R, et al. "The Leydig cell biomarker INSL3 as a predictor of age-related morbidity: Findings from the EMAS cohort." Front Endocrinol (Lausanne), 2022;13:1016107. PMID: 36425465.
- [clinical-trial] Albrethsen J, et al. "Serum Insulin-like Factor 3, Testosterone, and LH in Experimental and Therapeutic Testicular Suppression." J Clin Endocrinol Metab, 2023;108(11):2834-2839. PMID: 37235781.
- [review] Facondo P, et al. "INSL3: A Marker of Leydig Cell Function and Testis-Bone-Skeletal Muscle Network." Protein Pept Lett, 2020;27(12):1246-1252. PMID: 32981493.
- [review] Ivell R, et al. "Insulin-like peptide 3 (INSL3) is a major regulator of female reproductive physiology." Hum Reprod Update, 2018;24(6):639-651. PMID: 30204868.
Sources & Citations
Every study on this page was read from its PubMed record on October 30, 2026. Status comes from Drugs@FDA (openFDA), read the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.